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1.
Durmus, Naside Gozde.
Enhanced Efficacy of Nanotechnology-Driven Approaches
against Antibiotic-Resistant Biofilms in the Presence of
Metabolites.
Degree: PhD, Biomedical Engineering, 2013, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:320579/
► Antibiotic resistance and the lack of new antimicrobial therapies create significant challenges for the treatment of infections. Therefore, there is an urgent clinical need to…
(more)
▼ Antibiotic resistance and the lack of new
antimicrobial therapies create significant challenges for the
treatment of infections. Therefore, there is an urgent clinical
need to develop novel treatments targeting bacterial biofilms to
reduce the risk of infection, without resorting to antibiotics. The
goal of this thesis is, for the first time, to integrate two novel
approaches, i.e. nanotechnology and metabolic stimulation, to
eradicate
antibiotic-resistant biofilms. The metabolic
microenvironment of the biofilms has been manipulated to improve
the antibacterial properties of superparamagnetic iron oxide
nanoparticles (SPION) as well as nanorough device surfaces. First,
it has been shown that engineered nanoscale topographies provide
surfaces that are more resistant to bacterial growth than
conventional polyvinyl chloride (PVC). In addition, for the first
time, the presence of fructose on the nanorough PVC further
decreased the planktonic S. aureus growth and biofilm formation,
without use of any antibiotics. Moreover, a simple, broad-spectrum
and low-cost dual-sided approach which uses SPION in combination
with metabolites (i.e., fructose, glucose, and mannitol) has been
developed as an alternative to existing antibacterial strategies.
This strategy offers further improved efficacy of SPION against
persistent gram-positive and gram-negative bacteria infections by
manipulating the biofilm metabolic microenvironment, creating a new
nanotechnology-driven approach. Further, biofilm eradication by the
engineered SPION was significantly better than vancomycin, the
antibiotic of last resort. In addition, it has been demonstrated
that SPION conjugated with antibacterial silver salts exhibit
strong eradication properties against the
antibiotic-resistant
(MRSA) biofilms. Antibacterial properties of silver-conjugated
SPION were further improved when an external magnetic field was
applied as their magnetic core enabled them to penetrate into the
biofilms. This thesis, for the first time, highlighted the
importance of biofilm metabolic microenvironment for the
nanotechnology-driven approaches. It is envisioned that these
simple and inexpensive approaches could lead to novel alternative
treatments to the only current clinical option, vancomycin, which
MRSA has started to develop a
resistance towards. These novel
nanotechnology-driven approaches can lead to successful clinical
outcomes in terms of minimizing infections, longer medical device
lifetimes, and decreasing
antibiotic usage.
Advisors/Committee Members: Webster, Thomas (Director), Webster, Thomas (Reader), Tripathi, Anubhav (Reader), Sun, Shouheng (Reader), Morgan, Jeffrey (Reader), Tripathi, Anubhav (Director).
Subjects/Keywords: antibiotic resistance
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Chicago ·
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APA (6th Edition):
Durmus, N. G. (2013). Enhanced Efficacy of Nanotechnology-Driven Approaches
against Antibiotic-Resistant Biofilms in the Presence of
Metabolites. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:320579/
Chicago Manual of Style (16th Edition):
Durmus, Naside Gozde. “Enhanced Efficacy of Nanotechnology-Driven Approaches
against Antibiotic-Resistant Biofilms in the Presence of
Metabolites.” 2013. Doctoral Dissertation, Brown University. Accessed March 05, 2021.
https://repository.library.brown.edu/studio/item/bdr:320579/.
MLA Handbook (7th Edition):
Durmus, Naside Gozde. “Enhanced Efficacy of Nanotechnology-Driven Approaches
against Antibiotic-Resistant Biofilms in the Presence of
Metabolites.” 2013. Web. 05 Mar 2021.
Vancouver:
Durmus NG. Enhanced Efficacy of Nanotechnology-Driven Approaches
against Antibiotic-Resistant Biofilms in the Presence of
Metabolites. [Internet] [Doctoral dissertation]. Brown University; 2013. [cited 2021 Mar 05].
Available from: https://repository.library.brown.edu/studio/item/bdr:320579/.
Council of Science Editors:
Durmus NG. Enhanced Efficacy of Nanotechnology-Driven Approaches
against Antibiotic-Resistant Biofilms in the Presence of
Metabolites. [Doctoral Dissertation]. Brown University; 2013. Available from: https://repository.library.brown.edu/studio/item/bdr:320579/
2.
Vecchione, James J.
Using Chemical, Genetic, and Biochemical Approaches to
Understand and Circumvent Antibacterial Drug Resistance.
Degree: PhD, Chemistry, 2011, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:11186/
► The growing number of drug-resistant pathogenic bacteria is an impending public health crisis. Unfortunately, the rate at which pathogenic bacteria are developing resistance to our…
(more)
▼ The growing number of drug-resistant pathogenic
bacteria is an impending public health crisis. Unfortunately, the
rate at which pathogenic bacteria are developing
resistance to our
existing battery of anti-infective drugs is greater than the rate
at which new drugs are being developed. We pursued two
complementary strategies to address the problem of antibacterial
resistance. Firstly, we studied
resistance to indolmycin, a member
of a promising class of antibiotics known as the aminoacyl-tRNA
synthetase inhibitors. To elucidate the potential clinical utility
of indolmycin, we analyzed innate mechanisms of
resistance in
Streptomyces bacteria and assessed the distribution of indolmycin
resistance genes in the genomes of various bacterial genera. Our
combined genetic, biochemical, and bioinformatic approaches yielded
insights that are relevant to the development of aminoacyl-tRNA
synthetase inhibitors as antibacterial drugs. Secondly, we studied
ways to deactivate or circumvent
antibiotic resistance mechanisms
in bacteria. In particular, we demonstrated that indolmycin can
suppress multi-drug
resistance phenotypes via perturbation of
protein synthesis and showed that C-capped dipeptides can
potentiate the activity of chloramphenicol via inhibition of major
facilitator superfamily drug efflux pumps.
Advisors/Committee Members: Sello, Jason (Director), Suggs, J. William (Reader), Seto, Christopher (Reader).
Subjects/Keywords: Antibiotic Resistance
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APA ·
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APA (6th Edition):
Vecchione, J. J. (2011). Using Chemical, Genetic, and Biochemical Approaches to
Understand and Circumvent Antibacterial Drug Resistance. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:11186/
Chicago Manual of Style (16th Edition):
Vecchione, James J. “Using Chemical, Genetic, and Biochemical Approaches to
Understand and Circumvent Antibacterial Drug Resistance.” 2011. Doctoral Dissertation, Brown University. Accessed March 05, 2021.
https://repository.library.brown.edu/studio/item/bdr:11186/.
MLA Handbook (7th Edition):
Vecchione, James J. “Using Chemical, Genetic, and Biochemical Approaches to
Understand and Circumvent Antibacterial Drug Resistance.” 2011. Web. 05 Mar 2021.
Vancouver:
Vecchione JJ. Using Chemical, Genetic, and Biochemical Approaches to
Understand and Circumvent Antibacterial Drug Resistance. [Internet] [Doctoral dissertation]. Brown University; 2011. [cited 2021 Mar 05].
Available from: https://repository.library.brown.edu/studio/item/bdr:11186/.
Council of Science Editors:
Vecchione JJ. Using Chemical, Genetic, and Biochemical Approaches to
Understand and Circumvent Antibacterial Drug Resistance. [Doctoral Dissertation]. Brown University; 2011. Available from: https://repository.library.brown.edu/studio/item/bdr:11186/
3.
García Cazorla, Yolanda.
Inhibition of the conjugative traffic ATPase TrwD by fatty acid derivatives: Inhibición de la ATPasa conjugativa TrwD por derivados de ácidos grasos.
Degree: 2018, Universidad de Cantabria
URL: http://hdl.handle.net/10902/14718
► ABSTRACT: Antibiotic resistance has become a pressing public health concern. The main mechanism for the dissemination of resistance genes is the horizontal transfer during conjugation.…
(more)
▼ ABSTRACT:
Antibiotic resistance has become a pressing public health concern. The main mechanism for the dissemination of
resistance genes is the horizontal transfer during conjugation. Hence, the search for conjugation inhibitors (COINs) is paramount in the fight against the spread of resistances. In this pursuit, only unsaturated fatty acids had been described as COINs. Here, we define 2-bromopalmitic acid (2-BP) as a specific COIN. 2-BP is a palmitate analog without any unsaturation in its aliphatic chain which acts as inhibitor of many membrane-associated enzymes. The carboxylic group of COINs is essential for its effectivity. However, inhibition is not due to the presence of double or triple bonds in these compounds but, indirectly, by the conformation COINs can acquire upon binding to their molecular target.
We identify the VirB11 homolog in the conjugative plasmid R388, the traffic ATPase TrwD, as their molecular target. VirB11 form hexameric rings in which each monomer has a C-terminal catalytic region (CTD) and a N-terminal region that interacts with the cytoplasmic site of the membrane (NTD) connected both of them by a flexible linker. Biochemical and structural characterizations define a non-competitive inhibition where COINs bind to a pocket comprised by NTD and linker, preventing the pivoting movement of NTD over CTD which, in turn, result in a reduction of TrwD ATPase activity. Interestingly, COINs are liberally incorporated into bacterial membranes, replacing palmitic acid as the major component. We determine that TrwD binds palmitic acid, thus facilitating its interaction with the membrane. Altogether, our data suggest that COINs bind TrwD at a site that is otherwise occupied by palmitic acid, albeit they differ in the contacts involved in the interaction. As a result, COINs affect the interaction of TrwD with the membrane.
For a further understand of the conjugative process, we visualized the process in real time using fluorescent protein fusions to the main players in the conjugative system. Localization of the proteins suffers dramatic changes in the presence or absence of the rest of the component of the Type IV secretion system (T4SS). Moreover, by using fluorescent constructs of SeqA, a probe that binds hemimethylated DNA, we have found, surprisingly, that more than one event of conjugation takes place at a particular time. Additionally, we identify the formation of a weak complex between TrwD and the relaxase TrwC. TrwD presents structural homology to chaperones of the ClpB/Hsp 104 family, hence TrwD could play a chaperone activity during the transport of the pilot protein TrwC.
In short, our results do not only contribute to a better understanding of VirB11 proteins and the conjugative process but also may open a new avenue for the rational design of more potent and effective drugs to control dissemination of
antibiotic resistance genes.
Advisors/Committee Members: Cabezón Navarro, María Elena (advisor), Universidad de Cantabria (other).
Subjects/Keywords: Antibiotic resistance
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
García Cazorla, Y. (2018). Inhibition of the conjugative traffic ATPase TrwD by fatty acid derivatives: Inhibición de la ATPasa conjugativa TrwD por derivados de ácidos grasos. (Doctoral Dissertation). Universidad de Cantabria. Retrieved from http://hdl.handle.net/10902/14718
Chicago Manual of Style (16th Edition):
García Cazorla, Yolanda. “Inhibition of the conjugative traffic ATPase TrwD by fatty acid derivatives: Inhibición de la ATPasa conjugativa TrwD por derivados de ácidos grasos.” 2018. Doctoral Dissertation, Universidad de Cantabria. Accessed March 05, 2021.
http://hdl.handle.net/10902/14718.
MLA Handbook (7th Edition):
García Cazorla, Yolanda. “Inhibition of the conjugative traffic ATPase TrwD by fatty acid derivatives: Inhibición de la ATPasa conjugativa TrwD por derivados de ácidos grasos.” 2018. Web. 05 Mar 2021.
Vancouver:
García Cazorla Y. Inhibition of the conjugative traffic ATPase TrwD by fatty acid derivatives: Inhibición de la ATPasa conjugativa TrwD por derivados de ácidos grasos. [Internet] [Doctoral dissertation]. Universidad de Cantabria; 2018. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10902/14718.
Council of Science Editors:
García Cazorla Y. Inhibition of the conjugative traffic ATPase TrwD by fatty acid derivatives: Inhibición de la ATPasa conjugativa TrwD por derivados de ácidos grasos. [Doctoral Dissertation]. Universidad de Cantabria; 2018. Available from: http://hdl.handle.net/10902/14718

McMaster University
4.
Spanogiannopoulos, Peter.
Exploring Rifamycin Inactivation from the Soil Microbiome.
Degree: PhD, 2014, McMaster University
URL: http://hdl.handle.net/11375/16283
► Our battle against pathogens has become a challenge due to the rise in antibiotic resistance and the dwindling number of new antibiotics entering the clinic.…
(more)
▼ Our battle against pathogens has become a challenge due to the rise in antibiotic resistance and the dwindling number of new antibiotics entering the clinic. Most antibiotics owe their origins to soil bacteria, which have been producing these natural products for millennia. The rifamycins are products of actinomycetes and semisynthetic derivatives of these have been very successful in the clinic. Rifampin (RIF) has been a cornerstone agent against tuberculosis for over 50 years. In the clinic, pathogens typically develop RIF resistance by mutation of the drug. Nonetheless, a number of diverse RIF resistance mechanisms have been described, including enzymatic inactivation.
Environmental bacteria are multidrug resistant, likely due to sharing the same niche as antibiotic producers and represent a reservoir of ancient resistance determinants. Furthermore, these resistance determinants have been linked to pathogens. Exploring the antibiotic resistome, the collection of all antibiotic resistance determinants from the global microbiota, reveals the diversity and evolution of resistance and provides insight on vulnerabilities of our current antibiotics.
Herein, I describe a diverse collection of RIF-inactivating mechanisms from soil actinomycetes. I identified heretofore unknown RIF glycosyltransferase and RIF phosphotransferase genes (rgt and rph, respectively). RGT and RPH enzymes display broad rifamycin specificity and contribute to high-level resistance. Interestingly, RIF-sensitive Gram-positive pathogens are carriers of RPH, highlighting the existence of a ‘silent’ resistome in clinically relevant bacteria and emphasize the importance of studying resistance from environmental bacteria. Furthermore, I identified a conserved upstream DNA motif associated with RIF-inactivating genes from actinomycetes and demonstrate its role in RIF-responsive gene regulation. Finally, I explore the use of a RIF-resistance guided approach to identify novel rifamycin producing bacteria.
This study expands the rifamycin resistome, provides evidence of vulnerabilities of our current arsenal of rifamycin antibiotics, and offers a strategy to identify new members of this family natural product family.
Thesis
Doctor of Science (PhD)
Advisors/Committee Members: Wright, Gerard D., Biochemistry and Biomedical Sciences.
Subjects/Keywords: Antibiotic resistance; Microbiology
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Spanogiannopoulos, P. (2014). Exploring Rifamycin Inactivation from the Soil Microbiome. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/16283
Chicago Manual of Style (16th Edition):
Spanogiannopoulos, Peter. “Exploring Rifamycin Inactivation from the Soil Microbiome.” 2014. Doctoral Dissertation, McMaster University. Accessed March 05, 2021.
http://hdl.handle.net/11375/16283.
MLA Handbook (7th Edition):
Spanogiannopoulos, Peter. “Exploring Rifamycin Inactivation from the Soil Microbiome.” 2014. Web. 05 Mar 2021.
Vancouver:
Spanogiannopoulos P. Exploring Rifamycin Inactivation from the Soil Microbiome. [Internet] [Doctoral dissertation]. McMaster University; 2014. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11375/16283.
Council of Science Editors:
Spanogiannopoulos P. Exploring Rifamycin Inactivation from the Soil Microbiome. [Doctoral Dissertation]. McMaster University; 2014. Available from: http://hdl.handle.net/11375/16283
5.
Rashid, Muhammad Mahmudur.
Antibiotic resistance in different ecological niches in Bangladesh.
Degree: Ecology and Environmental Sciences, 2013, Umeå University
URL: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84193
► The rapid and wide scale environmental spread of multi-drug resistant bacteria is a seriousissue in recent years. Drug resistant bacteria have already occupied different…
(more)
▼ The rapid and wide scale environmental spread of multi-drug resistant bacteria is a seriousissue in recent years. Drug resistant bacteria have already occupied different ecologicalniches in many places, from wilderness to densely populated urban areas. To investigate theecological niches in Bangladesh samples were collected from wild migratory bird speciesOpen Bill Stork (Anastomus oscitans) and from the nearby water sources where these birdsvisited. A total of 76 E. coli isolates from the 170 OBS (Open Bill Stork) fecal samples and8 E. coli isolates from 3 river sources were isolated. Disk diffusion was used for checking thesusceptibility of the isolates against antibiotics that are common in human and veterinarymedicine in Bangladesh. It was found that 28.95%OBS and all water E. coli isolates wereresistant to at least one of the tested antibiotics. Common resistant phenotypes wereAmpicillin, Tetracycline, Aztreonam, Nalidixic Acid and Ciprofloxacin. Multi-drugresistance identified from 2.63%OBS and most of the water isolates. Very fewESBL(Extended Spectrum Beta-Lactamase) producing E. coli were found from OBS,whereas 50% of E. coli water isolates were ESBL producer, with all the ESBL producerspossessing the CTX-M-15 gene. The most concerning aspect of our findings was the presenceof human associated E. coli sequence types in water samples, for example ST156-complex156, ST10-complex10 and ST46. This study concludes the contaminationof environmental niches in Bangladesh by resistant bacteria.
Subjects/Keywords: Antibiotic resistance; Bangladesh
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APA ·
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MLA ·
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CSE |
Export
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APA (6th Edition):
Rashid, M. M. (2013). Antibiotic resistance in different ecological niches in Bangladesh. (Thesis). Umeå University. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84193
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rashid, Muhammad Mahmudur. “Antibiotic resistance in different ecological niches in Bangladesh.” 2013. Thesis, Umeå University. Accessed March 05, 2021.
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84193.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rashid, Muhammad Mahmudur. “Antibiotic resistance in different ecological niches in Bangladesh.” 2013. Web. 05 Mar 2021.
Vancouver:
Rashid MM. Antibiotic resistance in different ecological niches in Bangladesh. [Internet] [Thesis]. Umeå University; 2013. [cited 2021 Mar 05].
Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84193.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rashid MM. Antibiotic resistance in different ecological niches in Bangladesh. [Thesis]. Umeå University; 2013. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84193
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne
6.
Hardefeldt, Laura Yvonne.
Antimicrobial stewardship in Australian veterinary practices.
Degree: 2017, University of Melbourne
URL: http://hdl.handle.net/11343/198446
► Antimicrobial use by the veterinary profession has been coming under increasing scrutiny by medical, public health and government officials as the threat of antimicrobial resistance…
(more)
▼ Antimicrobial use by the veterinary profession has been coming under increasing scrutiny by medical, public health and government officials as the threat of antimicrobial resistance becomes increasingly clear. The World Health Organisation has described antimicrobial resistance as one of the major public health challenges of our time. It is clear that at least some drug-resistant pathogens have evolved under selective pressure from antimicrobial use in agriculture and may be contributing significantly to resistance in clinical setting. Antimicrobial stewardship is the selection of the most appropriate antimicrobial for a given disease in a given animal, with the aim of reducing the risk of adverse effects in that animal, and reducing the likelihood of developing resistance on an individual level, on a farm level and on a national level. Currently none of the core elements of antimicrobial stewardship are widely available for veterinarians in Australia, and there is very sparse data available on which to base an antimicrobial stewardship program. This research project aims to address this paucity of data. A range of research methods were used to assess detailed antimicrobial use by veterinarians in Australia and the enablers and barriers to antimicrobial stewardship. These included quantitative methods such as surveys and analysis of pet insurance data, and qualitative methods such as interviews and focus groups. While antimicrobials with low importance rating were predominately used in all species, under-dosing and inappropriate timing of antimicrobial therapy were common particularly in horses and cattle. Few veterinary practices in Australia had antimicrobial stewardship policies in place, or were using antimicrobial use guidelines. The key barriers to implementing antimicrobial stewardship programs were a lack of antimicrobial stewardship governance structures, client expectations and competition between practices, the cost of microbiological testing, and a lack of access to education, training and antimicrobial stewardship resources. The enablers were, firstly, concern for the role of veterinary antimicrobial use in development of antimicrobial resistance in humans, secondly , a sense of pride in the service provided, and thirdly , preparedness to change prescribing practices. This research culminated in the development of a proposed antimicrobial stewardship policy and procedure documents, to enable veterinarians to institute antimicrobial stewardship programs that suit their individual practice requirements. However, it is likely that governance changes will be necessary to compel veterinary practice owners to implement antimicrobial stewardship on a large scale.
Subjects/Keywords: antibiotic; antimicrobial resistance
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hardefeldt, L. Y. (2017). Antimicrobial stewardship in Australian veterinary practices. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/198446
Chicago Manual of Style (16th Edition):
Hardefeldt, Laura Yvonne. “Antimicrobial stewardship in Australian veterinary practices.” 2017. Doctoral Dissertation, University of Melbourne. Accessed March 05, 2021.
http://hdl.handle.net/11343/198446.
MLA Handbook (7th Edition):
Hardefeldt, Laura Yvonne. “Antimicrobial stewardship in Australian veterinary practices.” 2017. Web. 05 Mar 2021.
Vancouver:
Hardefeldt LY. Antimicrobial stewardship in Australian veterinary practices. [Internet] [Doctoral dissertation]. University of Melbourne; 2017. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11343/198446.
Council of Science Editors:
Hardefeldt LY. Antimicrobial stewardship in Australian veterinary practices. [Doctoral Dissertation]. University of Melbourne; 2017. Available from: http://hdl.handle.net/11343/198446

University of Oklahoma
7.
Lam, Anh.
ANTIBIOTIC COMBINATION THERAPY AGAINST MULTIDRUG-RESISTANT STAPHYLOCOCCUS EPIDERMIDIS BIOFILMS AND BROADENING ANTIBIOTIC SPECTRUM USING POLYETHYLENIMINE.
Degree: PhD, 2020, University of Oklahoma
URL: http://hdl.handle.net/11244/325287
► Antibiotic resistance (AR) is a serious growing threat around the globe. There has been no new antibiotic class developed in the past 30 years, while…
(more)
▼ Antibiotic resistance (AR) is a serious growing threat around the globe. There has been no new
antibiotic class developed in the past 30 years, while
antibiotic-resistant superbugs are emerging everywhere and becoming more and more life-threatening. In 2019, AR pathogens took away about 35,000 lives and infected over 2.8 million people a year in the United States alone. Experts predict that, by 2050, AR will be the top leading cause of death, claiming 10 million lives a year.
Motivated and dedicated to thousands of families who lose their loved ones each year to
antibiotic-resistant infections, our research lab studies the defense mechanisms of superbugs. Instead of finding a new
antibiotic, we study how to remove their
resistance using a potentiator called BPEI (branched polyethylenimine). BPEI is a chemical compound that can disable the
resistance factors of superbugs while traditional antibiotics (i.e. amoxicillin) can now actively target the vulnerable pathogens. It is called “combination therapy”. My initial specific contribution is study to fight one of the most commonly clinical isolates of Staph infections—multidrug-resistant Staphylococcus epidermidis. Previously known as a harmless commensal species on human skin, Staphylococcus epidermidis is now the first-ranking causative agent of hospital-related infections, with 24% mortality. It has become resistant to many antibiotics and thus acquired the name MRSE (Methicillin- Resistant Staphylococcus epidermidis). Additionally, MRSE bacteria can form dangerous biofilms – extra layers of self-made material – that protects them from antibiotics and helps them live on inanimate surfaces like medical devices for weeks to months. Persistent biofilms are also a leading cause of chronic wound infections. In the United States, a cost of $2 billion/year is estimated for S. epidermidis vascular-catheter-related bloodstream infections. This
resistance is mainly governed by a protein called PBP2a, which the susceptible Staph bacteria do not have. The protein PBP2a has a very low affinity for traditional β-lactam antibiotics, thereby making first-choice antibiotics ineffective. Here, the use of BPEI becomes effective because exposure to BPEI molecules inhibits the function of PBP2a of MRSE, and therefore making them susceptible to existing antibiotics.
Many experiments and analyses were conducted by using multiple biochemical techniques including microtiter plate assays, growth and time-killing curves, bacterial colony forming units, visible and fluorescence spectroscopies, electron microscopies, Fourier-transform infrared spectroscopy, and mass spectrometry. Not only being effective against MRSE, BPEI can also broaden
antibiotic spectrum against other bacterial species like MRSA, Pseudomonas aeruginosa, E. coli and their biofilms. Exact concentrations of each combination treatment were found for each bacterial strain. New mechanisms of action of BPEI against different bacteria and its effects on human inflammatory responses were also elucidated and reported in this…
Advisors/Committee Members: Rice, Charles (advisor), Nanny, Mark (committee member), Wu, Si (committee member), Yang, Zhibo (committee member), Shao, Yihan (committee member).
Subjects/Keywords: Antibiotic resistance; polyethylenimine
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lam, A. (2020). ANTIBIOTIC COMBINATION THERAPY AGAINST MULTIDRUG-RESISTANT STAPHYLOCOCCUS EPIDERMIDIS BIOFILMS AND BROADENING ANTIBIOTIC SPECTRUM USING POLYETHYLENIMINE. (Doctoral Dissertation). University of Oklahoma. Retrieved from http://hdl.handle.net/11244/325287
Chicago Manual of Style (16th Edition):
Lam, Anh. “ANTIBIOTIC COMBINATION THERAPY AGAINST MULTIDRUG-RESISTANT STAPHYLOCOCCUS EPIDERMIDIS BIOFILMS AND BROADENING ANTIBIOTIC SPECTRUM USING POLYETHYLENIMINE.” 2020. Doctoral Dissertation, University of Oklahoma. Accessed March 05, 2021.
http://hdl.handle.net/11244/325287.
MLA Handbook (7th Edition):
Lam, Anh. “ANTIBIOTIC COMBINATION THERAPY AGAINST MULTIDRUG-RESISTANT STAPHYLOCOCCUS EPIDERMIDIS BIOFILMS AND BROADENING ANTIBIOTIC SPECTRUM USING POLYETHYLENIMINE.” 2020. Web. 05 Mar 2021.
Vancouver:
Lam A. ANTIBIOTIC COMBINATION THERAPY AGAINST MULTIDRUG-RESISTANT STAPHYLOCOCCUS EPIDERMIDIS BIOFILMS AND BROADENING ANTIBIOTIC SPECTRUM USING POLYETHYLENIMINE. [Internet] [Doctoral dissertation]. University of Oklahoma; 2020. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11244/325287.
Council of Science Editors:
Lam A. ANTIBIOTIC COMBINATION THERAPY AGAINST MULTIDRUG-RESISTANT STAPHYLOCOCCUS EPIDERMIDIS BIOFILMS AND BROADENING ANTIBIOTIC SPECTRUM USING POLYETHYLENIMINE. [Doctoral Dissertation]. University of Oklahoma; 2020. Available from: http://hdl.handle.net/11244/325287

University of Minnesota
8.
Keppers, Adelle.
Characterization of Antibiotic Resistant Genes in Two Unique City Sewer Systems.
Degree: MS, Water Resources Science, 2020, University of Minnesota
URL: http://hdl.handle.net/11299/218657
► Sewer systems are known as point sources for the release of antibiotic resistance into the environment. Antibiotic resistance genes (ARGs) provide bacteria the ability to…
(more)
▼ Sewer systems are known as point sources for the release of antibiotic resistance into the environment. Antibiotic resistance genes (ARGs) provide bacteria the ability to fight antibiotics and are viewed as emerging contaminants in environmental waterways. To minimize the spread of ARGs to the environment, this study assessed the prevalence of ARGs in upstream sewer systems that feed into wastewater treatment plants (WWTPs) so that source control strategies can be developed to mitigate the spread of antibiotic resistance. Wastewaters were examined from two unique city sewer systems containing three source types: hospital, residential, and industrial. Twenty-nine ARGs, 3 integron-intergrases, and 4 metal resistance genes were quantified using conventional and microfluidic polymerase chain reactions. Bacterial community compositions were characterized using high-throughput 16S rRNA amplicon sequencing. We found the levels of ARGs and bacterial community compositions to be dependent on the source of wastewater, the city, and the season. The abundance of ARGs in hospital wastewater were relatively constant and associated with clinically relevant antibiotics. ARG abundance in residential wastewater showed seasonal variations with high levels in winter associated with outpatient antibiotics. High levels of integron-integrase genes, a proxy for horizontal gene transfer and anthropogenic impacts, were also observed in residential wastewaters. Based on these findings we suggest satellite treatment of ARGs at hospital and residential sources to reduce their loading to WWTPs and their inevitable release to the environment.
Subjects/Keywords: antibiotic resistance; antibiotic resistance genes; antibiotic resistant bacteria; antibiotics; sewage; wastewater
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APA (6th Edition):
Keppers, A. (2020). Characterization of Antibiotic Resistant Genes in Two Unique City Sewer Systems. (Masters Thesis). University of Minnesota. Retrieved from http://hdl.handle.net/11299/218657
Chicago Manual of Style (16th Edition):
Keppers, Adelle. “Characterization of Antibiotic Resistant Genes in Two Unique City Sewer Systems.” 2020. Masters Thesis, University of Minnesota. Accessed March 05, 2021.
http://hdl.handle.net/11299/218657.
MLA Handbook (7th Edition):
Keppers, Adelle. “Characterization of Antibiotic Resistant Genes in Two Unique City Sewer Systems.” 2020. Web. 05 Mar 2021.
Vancouver:
Keppers A. Characterization of Antibiotic Resistant Genes in Two Unique City Sewer Systems. [Internet] [Masters thesis]. University of Minnesota; 2020. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11299/218657.
Council of Science Editors:
Keppers A. Characterization of Antibiotic Resistant Genes in Two Unique City Sewer Systems. [Masters Thesis]. University of Minnesota; 2020. Available from: http://hdl.handle.net/11299/218657

University of Manitoba
9.
Fabra Prieto, Juan Camilo.
Synthesis and properties of tobramycinmoxifloxacin hybrid antibiotics linked at position C5 of tobramycin for overcoming resistance in Pseudomonas aeruginosa.
Degree: Chemistry, 2017, University of Manitoba
URL: http://hdl.handle.net/1993/32747
► This project focuses on developing tobramycin-moxifloxacin antibiotics, connected through an aliphatic tether, and evaluates its optimal length. The initial protocol had several shortcomings: the hybrid…
(more)
▼ This project focuses on developing tobramycin-moxifloxacin antibiotics, connected through an aliphatic tether, and evaluates its optimal length. The initial protocol had several shortcomings: the hybrid with a two-carbon linker could not be synthesized, the linkage of moxifloxacin to the aliphatic chain was done through the carboxylic group instead of the amino group, and the tobramycin moiety was decomposed into nebramine after being exposed to HCl. The protocol was improved by the introduction of a protecting group for preventing the synthesis of the ester and the sequential deprotection of tobramycin for avoiding its decomposition. Finally, 4,4’-bis(bromomethyl)biphenyl, which is a common molecular framework in drugs, was used as a linker to study the impact of rigidness on hybrid activity. The new protocol allowed the synthesis of protected hybrids in high yields; however, the purification of the final compounds was unsuccessful due to the presence of inorganic salts.
Advisors/Committee Members: Schweizer, Frank (Chemistry) (supervisor), Perreault, Helene (Chemistry).
Subjects/Keywords: Antibiotic Resistance; Pseudomonas Aeruginosa; Antibiotic Hybrids
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
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APA (6th Edition):
Fabra Prieto, J. C. (2017). Synthesis and properties of tobramycinmoxifloxacin hybrid antibiotics linked at position C5 of tobramycin for overcoming resistance in Pseudomonas aeruginosa. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/32747
Chicago Manual of Style (16th Edition):
Fabra Prieto, Juan Camilo. “Synthesis and properties of tobramycinmoxifloxacin hybrid antibiotics linked at position C5 of tobramycin for overcoming resistance in Pseudomonas aeruginosa.” 2017. Masters Thesis, University of Manitoba. Accessed March 05, 2021.
http://hdl.handle.net/1993/32747.
MLA Handbook (7th Edition):
Fabra Prieto, Juan Camilo. “Synthesis and properties of tobramycinmoxifloxacin hybrid antibiotics linked at position C5 of tobramycin for overcoming resistance in Pseudomonas aeruginosa.” 2017. Web. 05 Mar 2021.
Vancouver:
Fabra Prieto JC. Synthesis and properties of tobramycinmoxifloxacin hybrid antibiotics linked at position C5 of tobramycin for overcoming resistance in Pseudomonas aeruginosa. [Internet] [Masters thesis]. University of Manitoba; 2017. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/1993/32747.
Council of Science Editors:
Fabra Prieto JC. Synthesis and properties of tobramycinmoxifloxacin hybrid antibiotics linked at position C5 of tobramycin for overcoming resistance in Pseudomonas aeruginosa. [Masters Thesis]. University of Manitoba; 2017. Available from: http://hdl.handle.net/1993/32747

University of Waterloo
10.
Scott, Bradley.
Daptomycin: studies on its action mode and on bacterial resistance with model membranes.
Degree: 2016, University of Waterloo
URL: http://hdl.handle.net/10012/10480
► Bacterial resistance to antibiotics is one of the most serious problems facing medicine today. Recently, reports have appeared describing bacteria that are resistant to daptomycin…
(more)
▼ Bacterial resistance to antibiotics is one of the most serious problems facing medicine today. Recently, reports have appeared describing bacteria that are resistant to daptomycin (dap), an important antibiotic used against systemic infections caused by various Gram-positive (Gram+) bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This has caused considerable concern amongst the medical community. With few medicines being developed to replace them, research on antibiotics of last resort is imperative.
Dap is a branched, cyclic lipodepsipeptide consisting of a 10-amino acid macrolactone ring to which is attached an exocyclic tripeptide bearing a decanoyl acyl tail. Its activity is calcium-dependent. The action mode best substantiated involves the killing of bacteria through specific interaction with phosphatidylglycerol (PG) in their cell membranes, followed by the formation of oligomeric, cation-selective pores and dissipation of membrane potential. The successive steps of the action mode have been investigated using fluorescence-based assays in model membranes. The steps include, 1) calcium-mediated binding of monomers to PG at the outer leaflet; 2) formation of oligomers; 3) formation of pores through equilibration and alignment of oligomers across both membrane leaflets. The assay fluorophores include the intrinsically fluorescent kynurenine residue in dap, and various environmentally sensitive labels attached to dap by chemical modification.
The objective of this work was to investigate three topics: the means by which lysyl-phosphatidylglycerol (LPG) disrupts the action mode of dap, the means through which dap induces toxicity in humans, and the characterization of synthetic dap analogs, including an acyl-linked dimer. LPG is of interest because its increased formation is a known resistance mechanism for many cationic antimicrobial peptides (CAMPs); it is also correlated to resistance to dap specifically. A potential component in dap-induced toxicity is presence of phosphatidylserine (PS) in mammalian tissues. PS is a major phospholipid, and was investigated due to its anionic properties, which may emulate bacterial PG. The characterization of synthetic dap analogs allows for the study of the structure-activity relationship (SAR) of dap. The LPG, PS and characterization studies were pursued using the aforementioned fluorescence assays on a model membrane system using large unilamellar vesicles (LUV; liposomes), and antibacterial activity assays as needed. LUVs may be substituted with Bacillus subtilis L-forms (cell wall deficient bacteria) when necessary. Deviations in the assay results on LPG liposomes give insight into the action mode step(s) impeded in LPG-mediated bacterial resistance. The success or failure of the assays on PS membranes gives insight into the mechanism of toxicity via potential PS-mediated dap binding and permeabilization of mammalian cells. Characterization of the SAR of dap may lead to potential pharmacological improvements. Understanding these topics may also…
Subjects/Keywords: daptomycin; antibiotic; fluorescence; antibiotic resistance; L-form
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Scott, B. (2016). Daptomycin: studies on its action mode and on bacterial resistance with model membranes. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/10480
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Scott, Bradley. “Daptomycin: studies on its action mode and on bacterial resistance with model membranes.” 2016. Thesis, University of Waterloo. Accessed March 05, 2021.
http://hdl.handle.net/10012/10480.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Scott, Bradley. “Daptomycin: studies on its action mode and on bacterial resistance with model membranes.” 2016. Web. 05 Mar 2021.
Vancouver:
Scott B. Daptomycin: studies on its action mode and on bacterial resistance with model membranes. [Internet] [Thesis]. University of Waterloo; 2016. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10012/10480.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Scott B. Daptomycin: studies on its action mode and on bacterial resistance with model membranes. [Thesis]. University of Waterloo; 2016. Available from: http://hdl.handle.net/10012/10480
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Tech
11.
Thames, Callie H.
Excretion of Antibiotic Resistance Genes by Dairy Calves.
Degree: MS, Dairy Science, 2013, Virginia Tech
URL: http://hdl.handle.net/10919/19293
► Twenty-eight Holstein and crossbred calves of both genders were used to evaluate the effect of milk replacer antibiotics on abundance of selected antibiotic resistance genes…
(more)
▼ Twenty-eight Holstein and crossbred calves of both genders were used to evaluate the effect of milk replacer antibiotics on abundance of selected
antibiotic resistance genes (ARG) in the feces. Calves were blocked by breed, gender, and birth order, and assigned to one of three treatments at birth. Treatments were control (containing no antibiotics in the milk replacer), subtherapeutic (neomycin sulfate and oxytetracycline hydrochloride each fed at 10 mg/calf/d), and therapeutic (no antibiotics in the milk replacer until d 36, then neomycin sulfate and oxytetracycline hydrochloride each fed at 1000 mg/calf/d for 14 d). Calves were fed milk replacer twice daily at 0600 h and 1800 h. Fecal and respiratory scores and rectal temperatures were recorded daily. Calves were weighed at birth and weaning to calculate average daily gain. Beginning at six weeks of age fecal grab samples were collected from heifers at 0600 h, 1400 h, 2000 h, and 2400 h for 7 d, while bull calves were placed in metabolism crates for collection of all feces and urine. DNA was extracted from feces, and ARG corresponding to the tetracyclines (tetC, tetG, tetO, tetW, and tetX), macrolides (ermB, ermF), and sulfonamides (sul1, sul2) classes of antibiotics along with the class I integron gene, intI1, were measured by quantitative polymerase chain reaction (qPCR). No tetC or intI was detected. There was no significant effect of
antibiotic treatment on the absolute abundance (gene copies/ g wet manure) of any of the ARG except ermF, which was lower in the
antibiotic-treated calf manure probably because host bacterial cells carrying ermF were not resistant to tetracycline or neomycin. All ARG except tetC and intI were detectable in feces from 6 weeks onwards, and tetW and tetG significantly increased with time (P < 0.10), even in control calves. Overall, the majority of ARG analyzed for were present in the feces of the calves regardless of exposure to dietary
antibiotic. Feed antibiotics had little effect on the ARG monitored; other methods for reducing the ARG pool should also be investigated.
Advisors/Committee Members: Knowlton, Katharine F. (committeechair), James, Robert E. (committee member), Pruden, Amy (committee member).
Subjects/Keywords: antibiotic; antibiotic resistance gene; dairy calf
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Thames, C. H. (2013). Excretion of Antibiotic Resistance Genes by Dairy Calves. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/19293
Chicago Manual of Style (16th Edition):
Thames, Callie H. “Excretion of Antibiotic Resistance Genes by Dairy Calves.” 2013. Masters Thesis, Virginia Tech. Accessed March 05, 2021.
http://hdl.handle.net/10919/19293.
MLA Handbook (7th Edition):
Thames, Callie H. “Excretion of Antibiotic Resistance Genes by Dairy Calves.” 2013. Web. 05 Mar 2021.
Vancouver:
Thames CH. Excretion of Antibiotic Resistance Genes by Dairy Calves. [Internet] [Masters thesis]. Virginia Tech; 2013. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10919/19293.
Council of Science Editors:
Thames CH. Excretion of Antibiotic Resistance Genes by Dairy Calves. [Masters Thesis]. Virginia Tech; 2013. Available from: http://hdl.handle.net/10919/19293

Universiteit Utrecht
12.
Wekesa, A.N.
Prevalence of antibiotic resistance in East African Hospitals.
Degree: 2014, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/297497
► Introduction: Antibiotic resistance is a global burden, besides it is worse in low and middle-income countries where infectious diseases are still on the rise. This…
(more)
▼ Introduction:
Antibiotic resistance is a global burden, besides it is worse in low and middle-income countries where infectious diseases are still on the rise. This is occasioned by misuse of antibiotics.
Methods: We did a systematic literature review to assess the prevalence of
antibiotic resistance in major hospitals within the East African region.
Results: 20 articles were included in this review; they were published between 1997 and 2013. Of the 20 articles, 9 (45%) from Tanzania, 6 (30%) were from Kenya, 4 (20%), 1 (5%) from Uganda and Rwanda respectively. Overall
resistance rates varied in different studies. Prevalence for MRSA ranged from 0.4% to 84.1% as shown in table 1 while that of ESBL ranged from 9.9% to 81.9%
Conclusion: Antimicrobial
resistance is high in most major hospitals in East Africa
Advisors/Committee Members: Bonten, Prof. Marc, Bruijning- Verhagen, Ass. Prof. Patricia.
Subjects/Keywords: Antibiotic resistance; hospitals; East Africa
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wekesa, A. N. (2014). Prevalence of antibiotic resistance in East African Hospitals. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/297497
Chicago Manual of Style (16th Edition):
Wekesa, A N. “Prevalence of antibiotic resistance in East African Hospitals.” 2014. Masters Thesis, Universiteit Utrecht. Accessed March 05, 2021.
http://dspace.library.uu.nl:8080/handle/1874/297497.
MLA Handbook (7th Edition):
Wekesa, A N. “Prevalence of antibiotic resistance in East African Hospitals.” 2014. Web. 05 Mar 2021.
Vancouver:
Wekesa AN. Prevalence of antibiotic resistance in East African Hospitals. [Internet] [Masters thesis]. Universiteit Utrecht; 2014. [cited 2021 Mar 05].
Available from: http://dspace.library.uu.nl:8080/handle/1874/297497.
Council of Science Editors:
Wekesa AN. Prevalence of antibiotic resistance in East African Hospitals. [Masters Thesis]. Universiteit Utrecht; 2014. Available from: http://dspace.library.uu.nl:8080/handle/1874/297497

McMaster University
13.
King, Andrew M.
DISCOVERY AND CHARACTERIZATION OF NOVEL BETA-LACTAMASE INHIBITORS.
Degree: PhD, 2016, McMaster University
URL: http://hdl.handle.net/11375/19497
► The discovery of antibiotics and their subsequent clinical use has had a tremendous and beneficial impact on human health. The β-lactam antibiotics, which include penicillins,…
(more)
▼ The discovery of antibiotics and their subsequent clinical use has had a tremendous and beneficial impact on human health. The β-lactam antibiotics, which include penicillins, cephalosporins, carbapenems, and monobactams, constitute over half of the global antibiotic market. However, like all antibiotics, the β-lactams are susceptible to bacterial antibiotic resistance. One of the most disconcerting manifestations of bacterial resistance to β-lactam antibiotics is the evolution and dissemination of β-lactamases, enzymes able to chemically inactivate β-lactam antibiotics. These resistance determinants are the key contributing factor to extensively-drug resistant Gram-negative pathogens, for which we are already bereft of chemotherapeutic treatment options in some cases.
The coadministration of a β-lactamase inhibitor (BLI) with a β-lactam antibiotic is a proven therapeutic strategy to counter β-lactamase expression. Unfortunately, the emergence of both serine β-lactamases (SBLs) that are resistant to BLIs and metallo-β-lactamases (MBLs), which are intrinsically resistant to BLIs due to a discrete mechanism of β-lactam hydrolysis, threaten the efficacy of combination therapy. Notwithstanding this bacterial adaptation, the discovery and development of novel BLIs is an attractive strategy to evade resistance, as evidenced by the recent clinical approval of the diazabicyclooctane (DBO) SBL inhibitor, avibactam.
Herein, I describe efforts directed at understanding the mechanism of avibactam SBL inhibition. Furthermore, DBO derivatives are shown to display bifunctional properties in inhibiting both β-lactamases and the targets of β-lactam antibiotics, the penicillin-binding proteins. In addition to understanding the enzymology and chemical biology of DBOs, I describe two screening campaigns directed towards discovering inhibitors of MBLs, an unmet clinical need. Using target and cell-based screening of both synthetic and natural product chemical libraries, a fungal natural product inhibitor of clinically relevant MBLs was discovered and characterized.
This study expands our understanding of the mechanisms by which DBOs can be used to combat extensively drug-resistant Gram-negative pathogens. It also describes the discovery of a new natural product MBL inhibitor using a workflow that should be amenable to other resistance determinants. It’s hoped that these studies can contribute meaningfully to countering antibiotic resistance observed in clinical settings.
Thesis
Doctor of Philosophy (PhD)
Beta-lactam antibiotics like penicillin are a mainstay for treatment of bacterial infections. Bacterial resistance to these antibiotics threatens their utility and therefore new strategies are required to counter this phenomenon. Herein I describe efforts aimed at understanding new drugs and candidate drugs that act by inhibiting the function of enzymes produced by bacteria that are able to degrade beta-lactam antibiotics. Through the discovery of new molecules and an understanding of their chemical…
Advisors/Committee Members: Wright, Gerard D., Chemistry and Chemical Biology.
Subjects/Keywords: Chemical Biology; Antibiotic Resistance
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
King, A. M. (2016). DISCOVERY AND CHARACTERIZATION OF NOVEL BETA-LACTAMASE INHIBITORS. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/19497
Chicago Manual of Style (16th Edition):
King, Andrew M. “DISCOVERY AND CHARACTERIZATION OF NOVEL BETA-LACTAMASE INHIBITORS.” 2016. Doctoral Dissertation, McMaster University. Accessed March 05, 2021.
http://hdl.handle.net/11375/19497.
MLA Handbook (7th Edition):
King, Andrew M. “DISCOVERY AND CHARACTERIZATION OF NOVEL BETA-LACTAMASE INHIBITORS.” 2016. Web. 05 Mar 2021.
Vancouver:
King AM. DISCOVERY AND CHARACTERIZATION OF NOVEL BETA-LACTAMASE INHIBITORS. [Internet] [Doctoral dissertation]. McMaster University; 2016. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11375/19497.
Council of Science Editors:
King AM. DISCOVERY AND CHARACTERIZATION OF NOVEL BETA-LACTAMASE INHIBITORS. [Doctoral Dissertation]. McMaster University; 2016. Available from: http://hdl.handle.net/11375/19497

McMaster University
14.
Kelso, Jayne.
Characterizing the mechanism and regulation of a rifamycin monooxygenase in Streptomyces venezuelae.
Degree: MSc, 2016, McMaster University
URL: http://hdl.handle.net/11375/20423
► The rifamycins are a class of antibiotics which were once used almost exclusively to treat tuberculosis, but are currently receiving renewed interest. Resistance to rifamycins…
(more)
▼ The rifamycins are a class of antibiotics which were once used almost exclusively to treat tuberculosis, but are currently receiving renewed interest. Resistance to rifamycins is most commonly attributed to mutations in the drug target, RNA polymerase. Yet environmental isolates are also able to enzymatically inactivate rifamycins in a number of ways. Recently, rifamycin resistance determinants from the environment were found to be closely associated with a so called rifamycin associated element (RAE). The region containing the RAE from an environmental strain was shown to induce gene expression in the presence of rifamycins, hinting at an inducible system for rifamycin resistance. In this work, we examine the RAE from a model organism for Streptomyces genetics, Streptomyces venezuelae. We confirm that the promoter region containing the RAE upstream of a rifamycin monooxygenase rox is inducible by rifamycins. The strains of S. venezuelae generated in this work can be used in future genetic studies on the RAE.
As well, the rifamycin monooxygenase Rox was purified for the first time and characterized biochemically. The structure of Rox was obtained with and without the substrate rifampin. Steady state kinetics for the enzyme were determined with a number of substrates, and its ability to confer resistance to rifamycins was examined. Monooxygenated rifamycin SV compound was purified and structurally characterized by NMR analysis. We proposed an aromatic hydroxylase type mechanism for Rox, in which the enzyme hydroxylates the aromatic core of the rifamycin scaffold and causes a non-enzymatic C-N bond cleavage of the macrolactam ring. This is a new mechanism of rifamycin resistance, and sheds some light on the decomposition of rifamycins mediated by monooxygenation, which is still poorly understood.
Thesis
Master of Science (MSc)
Antibiotic resistance represents a major threat to global health. Infections that were once readily treatable are no longer so due to the rise in multidrug resistant bacteria. As our arsenal of effective antibiotics is depleted, new drugs are being discovered less and less frequently. This has caused the scientific community to get creative in coming up with treatments: trying combinations of antibiotics, using antibiotics which were once considered too toxic, and repurposing antibiotics for different bacteria.
Rifamycins are a class of antibiotics most commonly used in the treatment of tuberculosis. However, they are becoming more widely used as a result of antibiotic resistance. There are a number of different ways bacteria can become resistant to the harmful effects of rifamycins: by modifying the target so the drug can no longer bind to it, actively pumping the drug out of the cell, or by changing the drug in some way so it is no longer effective. Bacteria in the environment use antibiotics as a form of chemical warfare to gain an advantage over their neighbours; therefore, they have had millions of years to evolve very effective methods of antibiotic resistance. By surveying…
Advisors/Committee Members: Wright, Gerard D, Biochemistry and Biomedical Sciences.
Subjects/Keywords: Antibiotic resistance; Enzymology; Rifamycins
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kelso, J. (2016). Characterizing the mechanism and regulation of a rifamycin monooxygenase in Streptomyces venezuelae. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/20423
Chicago Manual of Style (16th Edition):
Kelso, Jayne. “Characterizing the mechanism and regulation of a rifamycin monooxygenase in Streptomyces venezuelae.” 2016. Masters Thesis, McMaster University. Accessed March 05, 2021.
http://hdl.handle.net/11375/20423.
MLA Handbook (7th Edition):
Kelso, Jayne. “Characterizing the mechanism and regulation of a rifamycin monooxygenase in Streptomyces venezuelae.” 2016. Web. 05 Mar 2021.
Vancouver:
Kelso J. Characterizing the mechanism and regulation of a rifamycin monooxygenase in Streptomyces venezuelae. [Internet] [Masters thesis]. McMaster University; 2016. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11375/20423.
Council of Science Editors:
Kelso J. Characterizing the mechanism and regulation of a rifamycin monooxygenase in Streptomyces venezuelae. [Masters Thesis]. McMaster University; 2016. Available from: http://hdl.handle.net/11375/20423
15.
Pawlowski, Andrew.
Diversity and Evolution of Antibiotic Resistomes.
Degree: PhD, 2017, McMaster University
URL: http://hdl.handle.net/11375/22808
► The relentless evolution of antibiotic resistance in pathogens is one of the most pressing medical concerns of the 21st century. Antibiotic resistance and antibiotic drugs…
(more)
▼ The relentless evolution of antibiotic resistance in pathogens is one of the most pressing medical concerns of the 21st century. Antibiotic resistance and antibiotic drugs originated in environmental bacteria, where they have been integral to their evolution for millions of years. The application of antibiotics in medicine and agriculture has selected for mobilization and dissemination of resistance genes in pathogens. Understanding their evolution here will aid in combating their evolution in pathogens.
This work expands the known mechanistic, functional, and genetic diversity of resistance (i.e. resistomes) in environmental bacteria. I systematically parse the extensively drug-resistant resistome of Paenibacillus sp. LC231, which was sampled from an underground ecosystem spatiotemporally isolated from the surface for over 4 Myr. Paenibacillus sp. LC231 was resistant to 26 of 40 drugs tested. Informatic annotation of resistance genes and functional genomes revealed 18 new resistance elements including five determinants without characterized homologs and three mechanisms not previously known to confer resistance.
I investigated the resistome of Brevibacillus brevis VM4 to study the relationship between species diversity and resistance diversity in the Paenibacillaceae family, which includes Paenibacillus sp. LC231. I found that resistome diversity does not correlate with species diversity, consistent with horizontal transfer of resistance genes.
In each of Paenibacillus sp. LC231 (MphI) and B. brevis VM4 (MphJ), I identified Mphs with unique substrate specifies. I identified the molecular determinants of substrate discrimination in MphI and in doing so, I developed a general strategy for understanding and predicting the functional evolution of resistance enzymes. Together, this work expands the known diversity of resistance that will enable better detection of resistance in pathogens.
Thesis
Doctor of Philosophy (PhD)
Infections caused by antibiotic resistant bacteria are a significant medical problem. Bacteria will always become resistant to antibiotic drugs. Understanding how resistance evolves is essential for increasing the effective lifetime of these drugs. Antibiotics have been naturally produced by bacteria for millions of years, which caused the spread of resistance in environmental bacteria. Medical and agricultural antibiotic use by humans caused resistance in environmental bacteria to transfer to pathogenic bacteria. My work expands the known causes of resistance in environmental bacteria so that we can better detect the causes of resistance in pathogens. In doing so, I demonstrate that multi-drug resistance is over 4 million years old and that environmental bacteria naturally transfer resistance genes. Furthermore, I develop a way to predict the evolution of new resistance functions by inferring their evolutionary histories.
Advisors/Committee Members: Wright, Gerard, Biochemistry and Biomedical Sciences.
Subjects/Keywords: Antibiotics; Antibiotic resistance; Microbial evolution
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pawlowski, A. (2017). Diversity and Evolution of Antibiotic Resistomes. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/22808
Chicago Manual of Style (16th Edition):
Pawlowski, Andrew. “Diversity and Evolution of Antibiotic Resistomes.” 2017. Doctoral Dissertation, McMaster University. Accessed March 05, 2021.
http://hdl.handle.net/11375/22808.
MLA Handbook (7th Edition):
Pawlowski, Andrew. “Diversity and Evolution of Antibiotic Resistomes.” 2017. Web. 05 Mar 2021.
Vancouver:
Pawlowski A. Diversity and Evolution of Antibiotic Resistomes. [Internet] [Doctoral dissertation]. McMaster University; 2017. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11375/22808.
Council of Science Editors:
Pawlowski A. Diversity and Evolution of Antibiotic Resistomes. [Doctoral Dissertation]. McMaster University; 2017. Available from: http://hdl.handle.net/11375/22808

Penn State University
16.
Harrow, Danielle Irene.
Greywater Reuse: Impact of Triclosan on Soil Microorganisms.
Degree: 2012, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/13928
► The use of greywater for irrigation results in the direct discharge of trace quantities of personal care products and antimicrobial agents to the environment. The…
(more)
▼ The use of greywater for irrigation results in the direct discharge of trace quantities of personal care products and antimicrobial agents to the environment. The presence of antibacterial compounds (e.g. triclosan) in greywater raises concerns regarding potential impacts of these materials on the environment and human health. Our research examined the impact of triclosan on soil microbial communities using soil filled pots irrigated with greywater (synthetic) only or greywater with triclosan. Functional diversity of the heterotrophic microbial community was assayed. Soil samples were cultured for viable heterotrophic bacteria and triclosan-resistant heterotrophic bacteria in the two treatments. Isolates were evaluated for
resistance to multiple antibiotics and used to quantify tetracycline
resistance genes. Under constant exposure, the community structure, showed two very distinct heterotrophic assemblages between soils treated with triclosan and the control soil. There were statistically significant increases in the number of heterotrophic organisms resistant to triclosan when the two soils were compared. The frequency of the tet a gene increased significantly in subsamples irrigated with greywater with triclosan as well as the proportion of bacterial isolates resistant to multiple antibiotics in these soil samples. Our results indicate that triclosan in greywater can have significant impacts on soil microbes. This in turn can affect the types of available nutrients within the soil. While antibacterial products may be present in trace concentrations in greywater, repeated exposure to soil organisms may be selecting for bacteria resistant to multiple types of antibiotics. Therefore, our results indicate that greywater should be treated to remove antibacterial agents before its use in lawn irrigation. Alternatively, the use of antibacterial containing products should be significantly reduced.
Advisors/Committee Members: Katherine H Baker, Thesis Advisor/Co-Advisor, Yen Chih Chen, Thesis Advisor/Co-Advisor, Shirley Elizabeth Clark, Thesis Advisor/Co-Advisor.
Subjects/Keywords: Triclosan; Antibiotic Resistance; Greywater
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Chicago ·
MLA ·
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APA (6th Edition):
Harrow, D. I. (2012). Greywater Reuse: Impact of Triclosan on Soil Microorganisms. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13928
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Harrow, Danielle Irene. “Greywater Reuse: Impact of Triclosan on Soil Microorganisms.” 2012. Thesis, Penn State University. Accessed March 05, 2021.
https://submit-etda.libraries.psu.edu/catalog/13928.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Harrow, Danielle Irene. “Greywater Reuse: Impact of Triclosan on Soil Microorganisms.” 2012. Web. 05 Mar 2021.
Vancouver:
Harrow DI. Greywater Reuse: Impact of Triclosan on Soil Microorganisms. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Mar 05].
Available from: https://submit-etda.libraries.psu.edu/catalog/13928.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Harrow DI. Greywater Reuse: Impact of Triclosan on Soil Microorganisms. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/13928
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
17.
Gumkowski, James.
Biochemical Characterization of Phylogenetically Diverse Homologs of the Antibiotic Resistance Protein Cfr and Related Genome Neighbors.
Degree: 2020, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/17593jdg298
► Radical S-adenosylmethionine (SAM) enzymes are one of the largest protein superfamilies identified to date, with more than 500,000 annotated members. While the functions of these…
(more)
▼ Radical S-adenosylmethionine (SAM) enzymes are one of the largest protein superfamilies identified to date, with more than 500,000 annotated members. While the functions of these enzymes vary widely, one of the most challenging chemical transformations that radical SAM enzymes are known to perform is methylation of unactivated carbon or phosphorous centers. The enzymes that catalyze these difficult reactions are known as the Class A-D radical SAM methyltransferases. The best characterized of the radical SAM methyltransferases are Class A, composed of RlmN and Cfr. RlmN is a housekeeping enzyme found in many bacteria that methylates rRNA and some tRNAs and is thought to promote translational fidelity. In contrast, Cfr is found in relatively few bacteria, largely Firmicutes, and its modification of rRNA has been shown to confer
antibiotic resistance to agents which target the exit tunnel of the peptidyl transferase center. It accomplishes this by appending a methyl group to the C8 position of A2503 (Escherichia coli numbering). cfr is of particular concern presently because it has been found on transposable elements and is appearing with increasing frequency in clinical settings.
The original aim of this work was to structurally characterize a member of the Cfr family, a goal which required finding sequences which diverge from model system Staphylococcus aureus Cfr. In chapter 2, four phylogenetically diverse Cfr homologs were isolated and characterized. Though none proved amenable to structural studies, biophysical and spectroscopic analyses revealed that all four homologs contained the radical SAM [4Fe-4S] cluster and were able to perform C8 methylation of a 155mer substrate mimic with varying efficiencies. These results suggest that Cfr-like activity associated with drug
resistance can be found in a diverse set of organisms, some of which are human pathogens. I also showed that the identity of the iron-sulfur cluster reductant can have a significant impact on activity. The small molecule reductant dithionite yielded more dimethylated product compared to a flavodoxin protein-based reducing system. This work underscores the importance of studying Cfr activity with native reductants, because reaction outcome can be influenced by the identity of the reducing system and the rate at which it operates relative to RNA product release.
In this dissertation I show that a clostridial Cfr homolog is an active rRNA methylase in vitro, a surprising observation given the lack of activity in other homologs from the clostridial clade. Additionally, the Mössbauer spectrum of Clostridioides difficile Cfr demonstrated the presence of a mononuclear iron cofactor in the C-terminal domain. In chapter 3, I use truncation variants to verify the biophysical and functional properties of this domain. When isolated separately, the domain binds a single iron (II) ion with rubredoxin-like properties. Addition of this domain in trans to a clostridial Cfr variant containing only the radical SAM domain did not affect activity. However,…
Advisors/Committee Members: Amie Kathleen Boal, Dissertation Advisor/Co-Advisor, Amie Kathleen Boal, Committee Chair/Co-Chair, Squire J Booker, Committee Member, Carsten Krebs, Committee Member, Ken Keiler, Outside Member, Philip C Bevilacqua, Program Head/Chair.
Subjects/Keywords: Antibiotic resistance; Cfr; KTR
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gumkowski, J. (2020). Biochemical Characterization of Phylogenetically Diverse Homologs of the Antibiotic Resistance Protein Cfr and Related Genome Neighbors. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/17593jdg298
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gumkowski, James. “Biochemical Characterization of Phylogenetically Diverse Homologs of the Antibiotic Resistance Protein Cfr and Related Genome Neighbors.” 2020. Thesis, Penn State University. Accessed March 05, 2021.
https://submit-etda.libraries.psu.edu/catalog/17593jdg298.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gumkowski, James. “Biochemical Characterization of Phylogenetically Diverse Homologs of the Antibiotic Resistance Protein Cfr and Related Genome Neighbors.” 2020. Web. 05 Mar 2021.
Vancouver:
Gumkowski J. Biochemical Characterization of Phylogenetically Diverse Homologs of the Antibiotic Resistance Protein Cfr and Related Genome Neighbors. [Internet] [Thesis]. Penn State University; 2020. [cited 2021 Mar 05].
Available from: https://submit-etda.libraries.psu.edu/catalog/17593jdg298.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gumkowski J. Biochemical Characterization of Phylogenetically Diverse Homologs of the Antibiotic Resistance Protein Cfr and Related Genome Neighbors. [Thesis]. Penn State University; 2020. Available from: https://submit-etda.libraries.psu.edu/catalog/17593jdg298
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
18.
Foley, Caitlin Ann.
Pennsylvania veterinarian perspectives of antibiotic use and antibiotic resistance.
Degree: 2014, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/21552
► Antibiotic drugs have been used to combat pathogenic bacteria for over fifty years and have proven to be one of the most valuable tools in…
(more)
▼ Antibiotic drugs have been used to combat pathogenic bacteria for over fifty years and have proven to be one of the most valuable tools in preserving human and animal health. With an increase in the use and availability of antibiotics,
antibiotic resistance has become a public health concern and has received much attention from government agencies, public interest groups, and the media. There is disagreement within the medical, veterinary, and regulatory communities regarding the veterinary use of antibiotics and associated risks to public health, and it is therefore important to investigate the many facets of
antibiotic use and encourage the development of educational programs and resources for all stakeholders.
This study focused on the use of a conceptual framework and survey instruments to explore the beliefs, knowledge and practices of veterinarians and to assess the current status of available educational resources pertaining to
antibiotic use and
antibiotic resistance. The primary purpose of this study was to investigate a wide variety of Pennsylvania veterinarians in order to identify relationships and differences between their perspectives, and facilitate the development of educational programs and strategies to benefit the field of veterinary medicine, animal industry stakeholders, and the public.
A non-experimental, descriptive-correlational research design was used to develop this study that focused on the population of all veterinarians licensed to practice medicine in Pennsylvania. Survey instruments were designed to capture the perspectives of two different groups of veterinarians: Group 1 – food/large animal vets, and Group 2 – all other vets. The surveys contained three sections to obtain demographic information, veterinarian perspectives of
antibiotic use and
antibiotic resistance across five perspectives dimensions (
Antibiotic Resistance,
Antibiotic Use, Veterinary Clientele, the General Public, and Veterinarian Practices), and perspectives of available educational resources. Veterinarians attending the PVMA Keystone conference completed a total of 66 usable paper surveys, and veterinarians contacted via email listservs completed 284 usable internet-based surveys.
Findings indicated that the two groups of veterinarians possessed varied perceptions across the five perspectives dimensions, and that significant differences in perspectives existed (p < .05). Data also indicated that the two groups of veterinarians recommended different types of
antibiotic drugs for disease treatment and prevention. Significant relationships existed between the select demographic variables (gender and years post-graduation from veterinary school) and the five perspectives dimensions. Findings also indicated the need for educational materials and resources regarding
antibiotic resistance for veterinarians, veterinary staff, veterinary clientele, and the general public; and concluded that veterinarians may be the best resource for educating their staff and clientele. Several modes for disseminating educational…
Advisors/Committee Members: Rama B Radhakrishna, Dissertation Advisor/Co-Advisor, Edgar Paul Yoder, Committee Member, John Ewing, Committee Member, Bhushan M Jayarao, Special Member.
Subjects/Keywords: veterinarian; perspectives; antibiotic resistance; livestock
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Foley, C. A. (2014). Pennsylvania veterinarian perspectives of antibiotic use and antibiotic resistance. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/21552
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Foley, Caitlin Ann. “Pennsylvania veterinarian perspectives of antibiotic use and antibiotic resistance.” 2014. Thesis, Penn State University. Accessed March 05, 2021.
https://submit-etda.libraries.psu.edu/catalog/21552.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Foley, Caitlin Ann. “Pennsylvania veterinarian perspectives of antibiotic use and antibiotic resistance.” 2014. Web. 05 Mar 2021.
Vancouver:
Foley CA. Pennsylvania veterinarian perspectives of antibiotic use and antibiotic resistance. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Mar 05].
Available from: https://submit-etda.libraries.psu.edu/catalog/21552.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Foley CA. Pennsylvania veterinarian perspectives of antibiotic use and antibiotic resistance. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/21552
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
19.
Lukwesa, Chileshe.
A survey of antibiotic prescribing patterns and in-vitro antibiotic susceptibility patterns at the University Teaching Hosptal, Lusaka,Zambia ,1998.
Degree: 2012, University of Zimbabwe
URL: http://dspace.unza.zm/handle/123456789/1566
► The development of drug resistance to common pathogens, has generated much concern in the medical community. The absence of an antibiotic policy at the University…
(more)
▼ The development of drug resistance to common pathogens, has generated much concern in the medical community. The absence of an antibiotic policy at the University Teaching Hospital (UTH), has resulted in a high frequency of antibiotic prescription and probable inappropriate use. This may have contributed to the increase in antibiotic resistance at the institution. The survey revealed a high frequency of 73 percent, with the four specialities: Medicine, Paediatrics, Surgery and Obstetrics and Gynaecology, 67 percent, 74 percent, 90 percent and 64 percent, respectively. Multiple antibiotic prescriptions was common (61 percent), adding to the cost of care. The most common antibiotic prescribed was Gentamicin and the common combination was Gentamicin-Penicillin. Common sites of infection were the lower respiratory tract, abdominal and wounds. Antibiotic resistance was high in the readily available cheaper antibiotics, namely Ampicillin (26%, 70%) , Cotrimoxazole (56%, 67%), Tetracycline (59%, 72%), and Chloramphenicol (8%, 50%) in Gram-positive and Gram-negative organisms, respectively, and as low as zero percent in the expensive ones, i.e. Cefotaxime (19%, 2%) and Ciprofloxacin (0%, 1%), respectively.
There is not much utilization of laboratory data and services in deciding on antibiotic use. Surveillance of bacterial resistance will provide health authorities,
physicians, and even pharmaceutical companies, with data on which the use of antibiotic may be rationalised.
Subjects/Keywords: Antiobiotics-Physiological effect; Antibiotic resistance
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lukwesa, C. (2012). A survey of antibiotic prescribing patterns and in-vitro antibiotic susceptibility patterns at the University Teaching Hosptal, Lusaka,Zambia ,1998. (Thesis). University of Zimbabwe. Retrieved from http://dspace.unza.zm/handle/123456789/1566
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lukwesa, Chileshe. “A survey of antibiotic prescribing patterns and in-vitro antibiotic susceptibility patterns at the University Teaching Hosptal, Lusaka,Zambia ,1998.” 2012. Thesis, University of Zimbabwe. Accessed March 05, 2021.
http://dspace.unza.zm/handle/123456789/1566.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lukwesa, Chileshe. “A survey of antibiotic prescribing patterns and in-vitro antibiotic susceptibility patterns at the University Teaching Hosptal, Lusaka,Zambia ,1998.” 2012. Web. 05 Mar 2021.
Vancouver:
Lukwesa C. A survey of antibiotic prescribing patterns and in-vitro antibiotic susceptibility patterns at the University Teaching Hosptal, Lusaka,Zambia ,1998. [Internet] [Thesis]. University of Zimbabwe; 2012. [cited 2021 Mar 05].
Available from: http://dspace.unza.zm/handle/123456789/1566.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lukwesa C. A survey of antibiotic prescribing patterns and in-vitro antibiotic susceptibility patterns at the University Teaching Hosptal, Lusaka,Zambia ,1998. [Thesis]. University of Zimbabwe; 2012. Available from: http://dspace.unza.zm/handle/123456789/1566
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Tech
20.
Willing, Brittany Faith.
Abundance of Antibiotic Resistance Genes in Feces Following Prophylactic and Therapeutic Intramammary Antibiotic Infusion in Dairy Cattle.
Degree: MS, Dairy Science, 2013, Virginia Tech
URL: http://hdl.handle.net/10919/24424
► Prophylactic and therapeutic antibiotic treatments have the potential to increase excretion of antibiotic resistance genes (ARGs) by dairy cattle through selection pressure on the gut…
(more)
▼ Prophylactic and therapeutic
antibiotic treatments have the potential to increase excretion of
antibiotic resistance genes (ARGs) by dairy cattle through selection pressure on the gut microbiome. The objective of these studies was to evaluate the effect of cephapirin benzathine administered prophylactically at the end of lactation and pirlimycin hydrochloride administered therapeutically during a clinical mastitis infection on the abundance and relative abundance of ARGs in dairy cow feces. For prophylactic treatment using cephapirin benzathine, nineteen end-of-lactation cows were used. Treatment cows (n = 9) received cephapirin benzathine as an intramammary infusion prior to dry-off, and control cows (n =10) received no antibiotics. All cows received an internal non-
antibiotic teat sealant. Fecal grab samples were collected for each cow on d -2 (baseline, used as covariate), d 1, 3, 5, 7, and once per week until d 49. Fecal samples were collected in sterile containers, then freeze-dried and
subject to DNA extraction. The abundance of ampC, blaCMY-2, ermB, sul1, tetO, tetW, integrase-specific gene int1, and 16S rRNA were quantified using quantitative polymerase chain reaction (qPCR). The genes ampC and blaCMY-2 encode
resistance to ß-lactam antibiotics, ermB to macrolides, sul1 to sulfonamides, tetO and tetW to tetracyclines, and int1 a class-1 integrase gene that facilitates horizontal transfer of ARGs across bacteria. The 16S rRNA gene was used as a representation of bacterial population. Absolute abundance was defined as number of ARG copies per gram of freeze-dried feces, while relative abundance was defined as ARG copy numbers per copy of 16S rRNA gene, which is indicative of the proportion of bacteria carrying ARGs. Non-normal data were logarithmically transformed and were statistically analyzed using PROC GLIMMIX in SAS 9.2. Abundance and relative abundance of sul1 and blaCMY-2 were below the limit of quantification in most samples and therefore not suitable for statistical comparisons. The int1 gene was not detectable in any sample. There were significant interactions between treatment and day for the abundance and relative abundance of ampC, tetO, and tetW. The abundance and relative abundance of ampC increased with time in control cows while remaining constant in
antibiotic treated cows through the dry period. Antibiotics may act to stabilize the gut microbiome in response to diet and housing changes. There was a significant main effect of treatment for ermB with a significantly greater proportion of bacteria carrying ermB in control cows when compared to
antibiotic treated cows. The tetracycline
resistance genes tetO and tetW behaved similarly with a significant treatment by day interaction for the abundance and relative abundance of both genes. The relative abundance of both tetO and tetW were greater in control cows when compared to
antibiotic treated cows on days 3, 5, 7, and 14. The abundance of both tetO and tetW
resistance genes increased in
antibiotic treated cows from day 1 to 49. There was also a…
Advisors/Committee Members: Knowlton, Katharine F. (committeechair), Pruden, Amy (committee member), Petersson-Wolfe, Christina S. (committee member).
Subjects/Keywords: antibiotic resistance gene; prophylactic; therapeutic
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Willing, B. F. (2013). Abundance of Antibiotic Resistance Genes in Feces Following Prophylactic and Therapeutic Intramammary Antibiotic Infusion in Dairy Cattle. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/24424
Chicago Manual of Style (16th Edition):
Willing, Brittany Faith. “Abundance of Antibiotic Resistance Genes in Feces Following Prophylactic and Therapeutic Intramammary Antibiotic Infusion in Dairy Cattle.” 2013. Masters Thesis, Virginia Tech. Accessed March 05, 2021.
http://hdl.handle.net/10919/24424.
MLA Handbook (7th Edition):
Willing, Brittany Faith. “Abundance of Antibiotic Resistance Genes in Feces Following Prophylactic and Therapeutic Intramammary Antibiotic Infusion in Dairy Cattle.” 2013. Web. 05 Mar 2021.
Vancouver:
Willing BF. Abundance of Antibiotic Resistance Genes in Feces Following Prophylactic and Therapeutic Intramammary Antibiotic Infusion in Dairy Cattle. [Internet] [Masters thesis]. Virginia Tech; 2013. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10919/24424.
Council of Science Editors:
Willing BF. Abundance of Antibiotic Resistance Genes in Feces Following Prophylactic and Therapeutic Intramammary Antibiotic Infusion in Dairy Cattle. [Masters Thesis]. Virginia Tech; 2013. Available from: http://hdl.handle.net/10919/24424

University of Illinois – Urbana-Champaign
21.
Garg, Neha.
Exploring and understanding lantibiotic biosynthesis.
Degree: PhD, 0318, 2014, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/46883
► The ribosome translates genomic information into structural and catalytic protein molecules. In addition to its role in protein synthesis, the ribosome also produces small non-catalytic…
(more)
▼ The ribosome translates genomic information into structural and catalytic protein molecules. In addition to its role in protein synthesis, the ribosome also produces small non-catalytic peptides that exert antimicrobial properties. The recent surge in the availability of genome sequences from a wide variety of bacterial sources has led to the rapid discovery of ribosomally-synthesized and post-translationally modified peptides (RiPPs). The biosynthetic machinery of RiPPs offers a new platform for the discovery and engineering of peptidic natural products. Although rapid advances have been made in elucidating biosynthetic pathways generating various RiPPs, investigations with respect to enzyme chemistry and action are still in their nascent stage. The novel chemistry via which post translational modifications (PTMs) are introduced into RiPPs emphasizes the synthetic potential found in nature. One such class of RiPPs are the lantibiotics, lanthipeptides with antimicrobial activity. The unifying PTMs found in lanthipeptides are thioether crosslinks, called lanthionine and methyl lanthionine. The crosslinks are formed via the dehydration of serine and threonine residues to dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues, respectively, followed by Michael-type addition of cysteines to the dehydrated residues. Nisin, a class I lantibiotic produced by Lactococcus lactis, is one of the oldest known antibiotics. In this study, we have developed a production strategy for class I lantibiotics in Escherichia coli and show successful production of nisin as a proof of concept.The dehydration reaction in class I lantibiotics, thiopeptides, and goadsporin is catalyzed by LanB or LanB-like proteins. Although LanB proteins have been studied since 1992, in vitro reconstitution of their dehydration activity has been elusive. Herein, we demonstrate the in vitro activity of NisB, the dehydratase involved in the biosynthesis of nisin. NisB requires glutamate, adenosine-5’-triphosphate, Mg2+, and the ribosomal/membrane fraction of bacterial cell extract to dehydrate its substrate peptide NisA. Mutation of 23 highly conserved residues of NisB identified a number of amino acids that are essential for dehydration activity. In addition, these mutagenesis studies identified three mutants, R786A, R826A, and H961A that result in multiple glutamylations of the NisA substrate. Glutamylation was observed both during E. coli co-expression of NisA with these mutants and during in vitro assays. Treatment of the glutamylated substrate with wild type NisB resulted in dehydrated NisA suggesting that the glutamylated peptide is an intermediate in dehydration. Collectively, these studies suggest that dehydration involves glutamylation of the side chains of Ser and Thr followed by elimination. The proposed reaction mechanism is unprecedented for lanthipeptide dehydration and these findings facilitate mechanistic investigations for other LanB proteins that are involved in the biosynthesis of lantibiotics, thiopeptides, and goadsporin.
Nisin is used…
Advisors/Committee Members: van der Donk, Wilfred A. (advisor), Nair, Satish K. (advisor), van der Donk, Wilfred A. (Committee Chair), Nair, Satish K. (committee member), Martinis, Susan A. (committee member), Zhao, Huimin (committee member).
Subjects/Keywords: Antibiotic resistance; Lantibiotic; Biosynthesis; Stereochemistry
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Garg, N. (2014). Exploring and understanding lantibiotic biosynthesis. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/46883
Chicago Manual of Style (16th Edition):
Garg, Neha. “Exploring and understanding lantibiotic biosynthesis.” 2014. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed March 05, 2021.
http://hdl.handle.net/2142/46883.
MLA Handbook (7th Edition):
Garg, Neha. “Exploring and understanding lantibiotic biosynthesis.” 2014. Web. 05 Mar 2021.
Vancouver:
Garg N. Exploring and understanding lantibiotic biosynthesis. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2014. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/2142/46883.
Council of Science Editors:
Garg N. Exploring and understanding lantibiotic biosynthesis. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2014. Available from: http://hdl.handle.net/2142/46883

University of Minnesota
22.
Lang, Kevin.
Transcriptional regulation of incompatibility type A/C plasmids.
Degree: PhD, Comparative and Molecular Biosciences, 2015, University of Minnesota
URL: http://hdl.handle.net/11299/174866
► Plasmids are extrachromosomal DNA elements that often carry beneficial phenotypes for the bacterial host. Incompatibility type A/C (IncA/C) plasmids are large (~100 ~ 200 kilobases…
(more)
▼ Plasmids are extrachromosomal DNA elements that often carry beneficial phenotypes for the bacterial host. Incompatibility type A/C (IncA/C) plasmids are large (~100 ~ 200 kilobases (kb)), conjugative plasmids that are carried by Gram-negative bacteria. IncA/C plasmids often carry numerous genes that confer resistance to antimicrobials and have been isolated from many types of bacteria that pose significant risks in both human and animal medicine. Although IncA/C plasmids have been described in the literature for many years, little is known about their basic biology. For the past decade, many fully sequenced IncA/C variants have been described. There has been a lack of work concerning core functions of these plasmids, such as, replication, conjugative transfer and maintenance. This dissertation focuses on how these plasmids are regulated on a transcriptional level. We used pAR060302, a prototypical IncA/C plasmid, to conduct several experiments investigating exactly what genes are transcribed and how different conditions affect their transcriptional landscape. RNA-Seq was used to understand how antimicrobial exposure can affect the way genes are expressed on IncA/C plasmids. We found that, under the conditions we tested, antimicrobials have little effect on the transcription of genes on pAR060302. However, this initial study was the first to explore genes carried IncA/C plasmids in terms of their expression. Further RNA-Seq experiments were carried out in several different bacterial genera all carrying the same IncA/C plasmid, pAR060302. These experiments attempted to characterize how a broad host-range plasmid, such as IncA/C, might be differentially regulated in different hosts. We found that only subtle changes occur in the expression of plasmid genes. Carriage of IncA/C plasmids was found to have diverse effects on chromosomal gene expression. Genes involved in 2-carbon metabolism in Escherichia coli are up-regulated due to plasmid carriage. Our results suggest that plasmid encoded factors might serve varying levels of importance depending on the host chromosomal background. Experiments were carried out on E. coli carrying plasmids with mutations in a group of predicted transcriptional regulators to determine their function. We identified the positive regulators of conjugative transfer in IncA/C plasmids, acaD and acaC. We also found a repressor of transfer, acr2, which encodes an H-NS-like protein. We further show that acr2 might regulate genes beyond those that are involved in conjugative transfer. This dissertation builds on our understanding on what mechanisms are important for the maintenance of large plasmids in Gram-negative bacteria. Understanding how plasmids might specifically tune host metabolism to improve competitive fitness would impact what evolutionary processes were involved in their emergence. Characterization of regulatory networks that govern core plasmid processes, such as conjugation, might assist in the development of new models of how these plasmids disseminate throughout bacterial…
Subjects/Keywords: antibiotic resistance; gene regulation; Plasmids
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lang, K. (2015). Transcriptional regulation of incompatibility type A/C plasmids. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/174866
Chicago Manual of Style (16th Edition):
Lang, Kevin. “Transcriptional regulation of incompatibility type A/C plasmids.” 2015. Doctoral Dissertation, University of Minnesota. Accessed March 05, 2021.
http://hdl.handle.net/11299/174866.
MLA Handbook (7th Edition):
Lang, Kevin. “Transcriptional regulation of incompatibility type A/C plasmids.” 2015. Web. 05 Mar 2021.
Vancouver:
Lang K. Transcriptional regulation of incompatibility type A/C plasmids. [Internet] [Doctoral dissertation]. University of Minnesota; 2015. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11299/174866.
Council of Science Editors:
Lang K. Transcriptional regulation of incompatibility type A/C plasmids. [Doctoral Dissertation]. University of Minnesota; 2015. Available from: http://hdl.handle.net/11299/174866
23.
Boudrioua, Abdelhakim.
Mode d'action moléculaire des peptides lasso sur la virulence et la résistance aux antibiotiques des bactéries pathogènes à Gram positif : Molecular mode of action of lasso peptides on virulence and antibiotic resistance of Gram-positive pathogenic bacteria.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2019, Normandie
URL: http://www.theses.fr/2019NORMC230
► La résistance aux antibiotiques est un problème de santé publique majeur. La mise sur le marché de nouveaux antibiotiques est rapidement suivie par l’apparition de…
(more)
▼ La résistance aux antibiotiques est un problème de santé publique majeur. La mise sur le marché de nouveaux antibiotiques est rapidement suivie par l’apparition de bactéries résistantes. Il est donc urgent de développer de nouvelles stratégies thérapeutiques.
Antibiotic resistance is a major public health concern. The increasing spread of antibiotic resistant bacteria has led to the investigation of new therapeutic strategies by developing next-generation drugs that target the virulence of the bacteria.
Advisors/Committee Members: Hartke, Axel (thesis director).
Subjects/Keywords: Staphylococcus; Enterococcus; Antibiotic resistance
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Boudrioua, A. (2019). Mode d'action moléculaire des peptides lasso sur la virulence et la résistance aux antibiotiques des bactéries pathogènes à Gram positif : Molecular mode of action of lasso peptides on virulence and antibiotic resistance of Gram-positive pathogenic bacteria. (Doctoral Dissertation). Normandie. Retrieved from http://www.theses.fr/2019NORMC230
Chicago Manual of Style (16th Edition):
Boudrioua, Abdelhakim. “Mode d'action moléculaire des peptides lasso sur la virulence et la résistance aux antibiotiques des bactéries pathogènes à Gram positif : Molecular mode of action of lasso peptides on virulence and antibiotic resistance of Gram-positive pathogenic bacteria.” 2019. Doctoral Dissertation, Normandie. Accessed March 05, 2021.
http://www.theses.fr/2019NORMC230.
MLA Handbook (7th Edition):
Boudrioua, Abdelhakim. “Mode d'action moléculaire des peptides lasso sur la virulence et la résistance aux antibiotiques des bactéries pathogènes à Gram positif : Molecular mode of action of lasso peptides on virulence and antibiotic resistance of Gram-positive pathogenic bacteria.” 2019. Web. 05 Mar 2021.
Vancouver:
Boudrioua A. Mode d'action moléculaire des peptides lasso sur la virulence et la résistance aux antibiotiques des bactéries pathogènes à Gram positif : Molecular mode of action of lasso peptides on virulence and antibiotic resistance of Gram-positive pathogenic bacteria. [Internet] [Doctoral dissertation]. Normandie; 2019. [cited 2021 Mar 05].
Available from: http://www.theses.fr/2019NORMC230.
Council of Science Editors:
Boudrioua A. Mode d'action moléculaire des peptides lasso sur la virulence et la résistance aux antibiotiques des bactéries pathogènes à Gram positif : Molecular mode of action of lasso peptides on virulence and antibiotic resistance of Gram-positive pathogenic bacteria. [Doctoral Dissertation]. Normandie; 2019. Available from: http://www.theses.fr/2019NORMC230

University of Debrecen
24.
Ullmann, Yotam.
New Pharmacological Approaches for Antibiotics Resistance
.
Degree: DE – Általános Orvostudományi Kar, University of Debrecen
URL: http://hdl.handle.net/2437/281197
Subjects/Keywords: Antibiotic Resistance
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ullmann, Y. (n.d.). New Pharmacological Approaches for Antibiotics Resistance
. (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/281197
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ullmann, Yotam. “New Pharmacological Approaches for Antibiotics Resistance
.” Thesis, University of Debrecen. Accessed March 05, 2021.
http://hdl.handle.net/2437/281197.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ullmann, Yotam. “New Pharmacological Approaches for Antibiotics Resistance
.” Web. 05 Mar 2021.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Vancouver:
Ullmann Y. New Pharmacological Approaches for Antibiotics Resistance
. [Internet] [Thesis]. University of Debrecen; [cited 2021 Mar 05].
Available from: http://hdl.handle.net/2437/281197.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Council of Science Editors:
Ullmann Y. New Pharmacological Approaches for Antibiotics Resistance
. [Thesis]. University of Debrecen; Available from: http://hdl.handle.net/2437/281197
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

University of Waterloo
25.
Couperus, Nathanael.
Estimation and Occurrence of Select Antimicrobials in the Grand River Watershed.
Degree: 2015, University of Waterloo
URL: http://hdl.handle.net/10012/9051
► Antimicrobials are pharmaceutically active compounds that destroy or inhibit the growth of bacteria, fungi, protozoa, or viruses. This diverse group of compounds, used in both…
(more)
▼ Antimicrobials are pharmaceutically active compounds that destroy or inhibit the growth of bacteria, fungi, protozoa, or viruses. This diverse group of compounds, used in both humans and livestock, are increasingly being detected in the environment, especially in soil and aquatic ecosystems. Their widespread environmental occurrence is being linked to the potential development of resistance traits in microorganisms, which is a serious threat to global health. Quantifying this health risk is difficult due to the lack of available data on the consumption of antimicrobials, as well as the varying regulations on their use and distribution. Further, the environmental fate and occurrence of these chemicals in watersheds is complex and poorly understood. The current research aims to address this knowledge gap by examining the occurrence and distribution of select antimicrobials in a watershed through modeling and empirical data collection (survey). It achieves this goal by addressing the following objectives: (1) to develop a mass load model for estimating the residual concentrations of veterinary antimicrobials; and (2) evaluate the occurrence and sources of select antimicrobials in surface waters. The Grand River Watershed, a mixed-use watershed in Southern Ontario, Canada, was selected as the study site.
The mass load model was used to estimate the residual concentrations of four veterinary antimicrobials (lincomycin, monensin, oxytetracycline, and sulfamethazine) in the soil and water matrices. Predicted antimicrobial concentrations ranged from 0.1 μg/kg (monensin and oxytetracycline) to 60 μg/kg in soil (sulfamethazine) and 37 pg/L (oxytetracycline) to 18 μg/L (sulfamethazine) in surface water. Estimated antimicrobial concentrations were highest in sub-basins with high livestock densities, with the highest predicted levels found in the Nith sub-basin where there is intensive livestock production.
For the occurrence survey in the Grand River Watershed, triplicate water samples were collected from 27 sites in the main channel, one location each in five tributaries, and seven wastewater treatment plant (WWTP) effluents. Temporal sampling was also performed in six additional sites (four in an agricultural tributary and two in the main channel). The water samples were analyzed for five antimicrobials (sulfamethazine, sulfamethoxazole, trimethoprim, lincomycin, and monensin), and three chemical indicators (venlafaxine, ibuprofen, and atrazine). In the main channel, measured concentrations of target analytes exhibited an increasing trend from the headwaters to downstream towards the discharge point to Lake Erie. Peak concentrations measured in the river water were 98 ± 8.8 ng/L for antimicrobials (sulfamethazine) and 146 ± 67 ng/L for the indicators (ibuprofen). In the effluents, the highest measured concentrations were 355 ± 126 ng/L for sulfamethoxazole and 349 ± 11 ng/L for ibuprofen. Atrazine was found at low concentrations throughout the river samples but was not found in the wastewater effluents. Lincomycin was…
Subjects/Keywords: Antimicrobial; Antibiotic Resistance; Estimation Model
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Couperus, N. (2015). Estimation and Occurrence of Select Antimicrobials in the Grand River Watershed. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/9051
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Couperus, Nathanael. “Estimation and Occurrence of Select Antimicrobials in the Grand River Watershed.” 2015. Thesis, University of Waterloo. Accessed March 05, 2021.
http://hdl.handle.net/10012/9051.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Couperus, Nathanael. “Estimation and Occurrence of Select Antimicrobials in the Grand River Watershed.” 2015. Web. 05 Mar 2021.
Vancouver:
Couperus N. Estimation and Occurrence of Select Antimicrobials in the Grand River Watershed. [Internet] [Thesis]. University of Waterloo; 2015. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10012/9051.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Couperus N. Estimation and Occurrence of Select Antimicrobials in the Grand River Watershed. [Thesis]. University of Waterloo; 2015. Available from: http://hdl.handle.net/10012/9051
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Queens University
26.
Krahn, Thomas.
Chromosomal Determinants of Aminoglycoside Resistance in Pseudomonas Aeruginosa
.
Degree: Microbiology and Immunology, 2012, Queens University
URL: http://hdl.handle.net/1974/7513
► Pseudomonas aeruginosa is an opportunistic pathogen found in soil and aquatic environments that possesses a broad range of intrinsic antibiotic resistance mechanisms, including a highly…
(more)
▼ Pseudomonas aeruginosa is an opportunistic pathogen found in soil and aquatic environments that possesses a broad range of intrinsic antibiotic resistance mechanisms, including a highly impermeable outer membrane and several RND-type efflux pumps that export a number of clinically relevant antibiotic classes. Chronic P. aeruginosa infections in cystic fibrosis (CF) patients gradually develop high levels of resistance to antimicrobial therapy due to conditions that favour the acquisition and selection of numerous chromosomal mutations, the nature of which are poorly understood. To identify chromosomal contributors to aminoglycoside resistance a P. aeruginosa transposon mutant library was screened for increases in aminoglycoside susceptibility. Six genes of interest (pstB, lptA, faoA, amgR, PA0392, and PA2798) were identified, the deletion of which meaningfully decreased aminoglycoside minimum inhibitory concentrations in wild-type P. aeruginosa. Combinations of gene deletions were constructed to determine if any of these genes contributed to aminoglycoside resistance via a common mechanism or whether they operated independently to promote intrinsic aminoglycoside resistance. In all cases, double deletion had an additive impact on aminoglycoside susceptibility, suggesting that each gene of interest contributes to resistance through an independent mechanism. Deletions in pstB, lptA, faoA, amgR, PA0392, and PA2798 were introduced into pan-aminoglycoside-resistant CF-lung isolates where they dramatically compromised aminoglycoside resistance, indicating that these genes also contribute to acquired aminoglycoside resistance in chronic P. aeruginosa infections. A fluorimetric assay was developed to measure aminoglycoside-induced membrane depolarization using the voltage sensitive probe DIBAC4(3). Gentamicin-induced membrane depolarization was found to be substantially increased in the amgR, pstB, and PA0392 mutant strains when compared to wild-type P. aeruginosa. These increases in depolarization paralleled declines in cell viability as measured by a gentamicin killing assay, suggesting that the cytoplasmic membranes of these mutant strains are more sensitive to the membrane perturbing effects of aminoglycoside-induced mistranslated proteins, and supporting a role for the disruption of the selective barrier of the cytoplasmic membrane in the bactericidal activity of the aminoglycosides. This study describes novel contributors to intrinsic and acquired aminoglycoside resistance in P. aeruginosa, and highlights the importance of membrane functions in resisting these activities.
Subjects/Keywords: Antibiotic Resistance
;
Pseudomonas Aeruginosa
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Krahn, T. (2012). Chromosomal Determinants of Aminoglycoside Resistance in Pseudomonas Aeruginosa
. (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/7513
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Krahn, Thomas. “Chromosomal Determinants of Aminoglycoside Resistance in Pseudomonas Aeruginosa
.” 2012. Thesis, Queens University. Accessed March 05, 2021.
http://hdl.handle.net/1974/7513.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Krahn, Thomas. “Chromosomal Determinants of Aminoglycoside Resistance in Pseudomonas Aeruginosa
.” 2012. Web. 05 Mar 2021.
Vancouver:
Krahn T. Chromosomal Determinants of Aminoglycoside Resistance in Pseudomonas Aeruginosa
. [Internet] [Thesis]. Queens University; 2012. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/1974/7513.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Krahn T. Chromosomal Determinants of Aminoglycoside Resistance in Pseudomonas Aeruginosa
. [Thesis]. Queens University; 2012. Available from: http://hdl.handle.net/1974/7513
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
27.
Conwell, Michael.
Transfer of antibiotic resistances between enterococci in biofilm.
Degree: PhD, 2018, Ulster University
URL: https://ulster.pure.elsevier.com/en/studentTheses/2dbef13a-4f51-4a8a-87d7-0377602c86e6
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.793639
► Antibiotic resistance is an urgent and increasing problem in human and animal healthcare. While it is recognised that the environment must provide an opportunity for…
(more)
▼ Antibiotic resistance is an urgent and increasing problem in human and animal healthcare. While it is recognised that the environment must provide an opportunity for resistance to develop and spread, direct evidence for the mechanisms involved is still lacking. This research utilised enterococci from an agrarian environment to demonstrate horizontal gene transfer (HGT) of antibiotic resistance genes in specific reservoirs. Screening a biobank of over 600 environmental isolates referencing previous partial characterisation data resulted in the selection of eleven Enterococcus faecalis and four E. faecium strains that exhibited potential for conjugation via a pheromone-dependent pathway. These isolates had prolific and diverse antimicrobial resistance profiles. Conjugal transfer of antibiotic resistance phenotypes was determined using a solid agar mating method followed by a standard antibiotic selection test resulting in different transfer patterns. Multiple gene transfer was observed in single reactions. An interspecies conjugal transfer of vancomycin resistance from E. faecalis to E. faecium was identified while the remaining reactions were within the same species. Transfer efficiencies ranging from 2 × 10−1 to 2.3 × 10−5 were determined. Interspecies transfer of vancomycin resistance among environmental isolates of enterococci had not previously been characterised, along with alternating transfer of different determinants from the same donor to different recipients. In certain cases, antimicrobial resistance to non-transferred resistance was elevated in transconjugants (T1, T2 and T4). A novel biofilm apparatus model, based upon a Gene Frame, was developed to allow nondestructive analysis of Enterococcus biofilm. Fluorescently tagged Concanavalin A was used to label extracellular matrix material and bacteria were identified by fluorescent in situ hybridization (FISH) and DAPI staining. This unique model was more reproducible X than standard biofilm assays and it proved to be flexible in that it was adapted to identify antibiotic resistance genes. This novel system was used to demonstrate that interspecies transfer of vancomycin resistance takes place in bacterial biofilms, which are considered to be the natural state for environmental bacteria. Additionally, multiprobe FISH targeted to vanA on mobile elements demonstrated for the first-time vancomycin staining inside enterococcal biofilm. Another potential reservoir of bacteria in an aquatic environment is the freshwater sponge. Enterococcus conjugation experiments were performed on Ephydatia fluviatilis and Spongilla lacustris, two sponge species that exist in similar geographical topography to where the enterococci were isolated. Enterococci were shown to bind to sponge material and HGT of vancomycin resistance was demonstrated in both sponge species by the modified FISH assay and by direct antibiotic selection methods. Overall, this thesis highlights that enterococci of environmental origin are capable of transferring important resistance determinants in and out…
Subjects/Keywords: Biofilm; Antibiotic Resistance; Enterococci
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Conwell, M. (2018). Transfer of antibiotic resistances between enterococci in biofilm. (Doctoral Dissertation). Ulster University. Retrieved from https://ulster.pure.elsevier.com/en/studentTheses/2dbef13a-4f51-4a8a-87d7-0377602c86e6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.793639
Chicago Manual of Style (16th Edition):
Conwell, Michael. “Transfer of antibiotic resistances between enterococci in biofilm.” 2018. Doctoral Dissertation, Ulster University. Accessed March 05, 2021.
https://ulster.pure.elsevier.com/en/studentTheses/2dbef13a-4f51-4a8a-87d7-0377602c86e6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.793639.
MLA Handbook (7th Edition):
Conwell, Michael. “Transfer of antibiotic resistances between enterococci in biofilm.” 2018. Web. 05 Mar 2021.
Vancouver:
Conwell M. Transfer of antibiotic resistances between enterococci in biofilm. [Internet] [Doctoral dissertation]. Ulster University; 2018. [cited 2021 Mar 05].
Available from: https://ulster.pure.elsevier.com/en/studentTheses/2dbef13a-4f51-4a8a-87d7-0377602c86e6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.793639.
Council of Science Editors:
Conwell M. Transfer of antibiotic resistances between enterococci in biofilm. [Doctoral Dissertation]. Ulster University; 2018. Available from: https://ulster.pure.elsevier.com/en/studentTheses/2dbef13a-4f51-4a8a-87d7-0377602c86e6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.793639

Georgia Tech
28.
Kim, Minjae.
Genomic Investigations of the Role of Disinfectant-Induced Antibiotic Resistance for Public Health.
Degree: PhD, Civil and Environmental Engineering, 2019, Georgia Tech
URL: http://hdl.handle.net/1853/63504
► Microorganisms occupy almost every habitat on earth such as soils, ocean, freshwater, and engineered systems (e.g., wastewater treatment systems), and are often associated with other…
(more)
▼ Microorganisms occupy almost every habitat on earth such as soils, ocean, freshwater, and engineered systems (e.g., wastewater treatment systems), and are often associated with other multicellular organisms. Their communities play various important roles in controlling the biogeochemical cycles, and human and animal wellbeing (e.g., food fermentation, preventing infectious disease agents). Even though the great majority of microorganisms are beneficial to human and animal life and health, there have been rising public health concerns such as the recent emergence and spreading of antimicrobial resistant pathogens.
The advent of high-throughput sequencing technology and the accompanying development of bioinformatics tools for the analysis of the resulting sequence data in the past decade have enabled the high throughput characterization of the complex microbiota in various environments. Rapid analysis of microbial isolate genomes from various environments through whole-genome sequencing (WGS) has provided new insights into their ecological roles, identified novel species, and tracked the source of disease outbreak. For example, the identification of genomic islands (GIs) and single nucleotide polymorphisms (SNPs) among genomes of the same species can be used to identify the genomic determinants of antimicrobial
resistance and to distinguish highly virulent from commensal strains of the species. Moreover, the rise of metagenomics (sequencing of the total microbial community DNA extracted from a target sample) has transformed our understanding of the microbial ecology and physiology of diverse ecosystems, by bypassing the need to isolate the organisms in the lab, a major limitation of traditional lab-based approaches.
Although a substantial amount of work has been done in public and environmental health microbiology with omics techniques, there are still unresolved or debatable issues remaining. In this thesis, we combined traditional, culture-based laboratory techniques with cutting-edge, culture-independent omics tools to provide insight into several important research questions. Specifically, in chapter 2, we did metagenomic analysis of bioreactors, MinION-based long-read sequencing of microbial isolates, and molecular cloning to provide molecular evidence that exposure to the widely used disinfectant benzalkonium chlorides (BAC), a member of QAC family, can co-select for
antibiotic resistant bacteria. These results contribute toward solving a high debatable issue in the literature for the past two decades, i.e., whether or not exposure to disinfectants promotes
antibiotic resistance. In chapter 3, we assessed the effects of BAC-exposure of two different Pseudomonas aeruginosa strains, i.e., one pre-exposed to sub-inhibitory concentrations of BAC for three years vs. its non-exposed counterpart, to increasing concentrations of BAC for about two hundred generations (1-2 months) and applied transcriptomic analysis to reveal molecular mechanisms for the microbial BAC
resistance at the whole cell level, including…
Advisors/Committee Members: Konstantinidis, Konstantinos T. (advisor), Pavlostathis, Spyros G. (committee member), Brown, Joe (committee member), Stewart, Frank (committee member), Levy, Karen (committee member).
Subjects/Keywords: Antibiotic Resistance; Sanitation Interventions
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kim, M. (2019). Genomic Investigations of the Role of Disinfectant-Induced Antibiotic Resistance for Public Health. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/63504
Chicago Manual of Style (16th Edition):
Kim, Minjae. “Genomic Investigations of the Role of Disinfectant-Induced Antibiotic Resistance for Public Health.” 2019. Doctoral Dissertation, Georgia Tech. Accessed March 05, 2021.
http://hdl.handle.net/1853/63504.
MLA Handbook (7th Edition):
Kim, Minjae. “Genomic Investigations of the Role of Disinfectant-Induced Antibiotic Resistance for Public Health.” 2019. Web. 05 Mar 2021.
Vancouver:
Kim M. Genomic Investigations of the Role of Disinfectant-Induced Antibiotic Resistance for Public Health. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/1853/63504.
Council of Science Editors:
Kim M. Genomic Investigations of the Role of Disinfectant-Induced Antibiotic Resistance for Public Health. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/63504

University of Sydney
29.
Moran, Robert A.
Characterisation of plasmids in commensal Escherichia coli from healthy Australian adults
.
Degree: 2018, University of Sydney
URL: http://hdl.handle.net/2123/18199
► Commensal Escherichia coli are thought to be an important reservoir of antibiotic resistance determinants, which are disseminated by the actions of translocatable genetic elements and…
(more)
▼ Commensal Escherichia coli are thought to be an important reservoir of antibiotic resistance determinants, which are disseminated by the actions of translocatable genetic elements and plasmids that can transfer horizontally between cells. However, the plasmids of commensal E. coli and their role in the global spread of resistance genes have not been examined in detail. Here, 16 E. coli strains isolated from a single subject over a 700-day period were added to an existing, diverse collection of E. coli from healthy Australians. The complete collection contains 111 strains, with 51 resistant to one or more antibiotics. The plasmid content of the collection was examined using PCR and sequence-based approaches, revealing that plasmid replicons are far more diverse than previously appreciated. The presence of identical FII, FIB and several different I-complex replicons in unrelated strains from different subjects provided evidence for the dissemination of these types. Furthermore, several different plasmids were shown to have transferred between strains in the gastrointestinal tracts of healthy subjects in the absence of antibiotic selection. The complete sequences of plasmids of various types from this collection that contain antibiotic or heavy metal resistance genes were assembled. Their backbones were defined and used to query the GenBank database, revealing that most were also found in strains associated with infections, and that these plasmids are globally disseminated. The evolution of plasmid lineages via recombination and the actions of translocatable elements was traced, revealing how each lineage acquired and accumulated resistance determinants. This study has demonstrated that plasmids found in commensal E. coli are also found in strains that cause infections. The plasmids are acquiring antibiotic resistance genes and disseminating amongst strains, with the healthy human gastrointestinal tract an important site for their persistence and transfer.
Subjects/Keywords: Escherichia coli;
Plasmid;
antibiotic resistance
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Moran, R. A. (2018). Characterisation of plasmids in commensal Escherichia coli from healthy Australian adults
. (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/18199
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Moran, Robert A. “Characterisation of plasmids in commensal Escherichia coli from healthy Australian adults
.” 2018. Thesis, University of Sydney. Accessed March 05, 2021.
http://hdl.handle.net/2123/18199.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Moran, Robert A. “Characterisation of plasmids in commensal Escherichia coli from healthy Australian adults
.” 2018. Web. 05 Mar 2021.
Vancouver:
Moran RA. Characterisation of plasmids in commensal Escherichia coli from healthy Australian adults
. [Internet] [Thesis]. University of Sydney; 2018. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/2123/18199.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Moran RA. Characterisation of plasmids in commensal Escherichia coli from healthy Australian adults
. [Thesis]. University of Sydney; 2018. Available from: http://hdl.handle.net/2123/18199
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Sydney
30.
Limantoro, Christina.
Gallium nanoparticle as an antimicrobial agent to combat antibiotic resistance
.
Degree: 2020, University of Sydney
URL: http://hdl.handle.net/2123/23171
► Since they were first discovered, antibiotics have been used to fight bacterial infections and save millions of lives. However, their increased use has allowed for…
(more)
▼ Since they were first discovered, antibiotics have been used to fight bacterial infections and save millions of lives. However, their increased use has allowed for the development of antibiotic resistant pathogens, which reduces their efficacy and threatens the accomplishments of modern medicine. The development of a new agent represents a major unmet clinical societal need. Metals are increasingly becoming considered as an alternative antimicrobial agent, and gallium in particular has gained a lot of attention in recent years. Whilst their antimicrobial activity has been demonstrated against a variety of bacterial pathogens and biofilms, their translation into the clinical setting is partly hindered by its low bioavailability. To address this issue, this project aimed to use nanotechnology to develop gallium-based nano-formulations. Several synthesis methods, namely the heat-up method, hot-injection and flame spray pyrolysis were successfully used to synthesise different classes of gallium nanoparticle. The heat-up method produced gallium nanoparticles with low uniformity and was difficult to reproduce. As such, only hot-injection and flame spray pyrolysis synthesised gallium nanoparticles were further investigated for their antimicrobial activity and toxicity. Despite undetected minimum inhibitory concentrations, gallium nanoparticles showed activity towards biofilm. They altered biofilm morphology and reduced pyocyanin production, which relates to the pathogen’s virulence factor. The results indicate the potential of gallium nanoparticle for development as an antimicrobial agent
Subjects/Keywords: nanoparticle;
antimicrobial;
antibiotic resistance
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APA (6th Edition):
Limantoro, C. (2020). Gallium nanoparticle as an antimicrobial agent to combat antibiotic resistance
. (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/23171
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Limantoro, Christina. “Gallium nanoparticle as an antimicrobial agent to combat antibiotic resistance
.” 2020. Thesis, University of Sydney. Accessed March 05, 2021.
http://hdl.handle.net/2123/23171.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Limantoro, Christina. “Gallium nanoparticle as an antimicrobial agent to combat antibiotic resistance
.” 2020. Web. 05 Mar 2021.
Vancouver:
Limantoro C. Gallium nanoparticle as an antimicrobial agent to combat antibiotic resistance
. [Internet] [Thesis]. University of Sydney; 2020. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/2123/23171.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Limantoro C. Gallium nanoparticle as an antimicrobial agent to combat antibiotic resistance
. [Thesis]. University of Sydney; 2020. Available from: http://hdl.handle.net/2123/23171
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
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