subject:(antibiotic)

University of Georgia

1. Tillman, Glenn Edward. Microfloral profile of the broiler midgut intestinal tract and cecum after addition of lupulone (hop β-acid) through drinking water and challenge with Clostridium perfringens.

Degree: MS, Toxicology, 2007, University of Georgia

URL: http://purl.galileo.usg.edu/uga_etd/tillman_glenn_e_200705_ms

► The use of antibiotic growth promotants in poultry rearing is a public health concern due to antibiotic resistance in bacteria and the harborage of resistance… (more)

Subjects/Keywords: Antibiotic Alternative

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APA (6^th Edition):

Tillman, G. E. (2007). Microfloral profile of the broiler midgut intestinal tract and cecum after addition of lupulone (hop β-acid) through drinking water and challenge with Clostridium perfringens. (Masters Thesis). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/tillman_glenn_e_200705_ms

Chicago Manual of Style (16^th Edition):

Tillman, Glenn Edward. “Microfloral profile of the broiler midgut intestinal tract and cecum after addition of lupulone (hop β-acid) through drinking water and challenge with Clostridium perfringens.” 2007. Masters Thesis, University of Georgia. Accessed January 18, 2020. http://purl.galileo.usg.edu/uga_etd/tillman_glenn_e_200705_ms.

MLA Handbook (7^th Edition):

Tillman, Glenn Edward. “Microfloral profile of the broiler midgut intestinal tract and cecum after addition of lupulone (hop β-acid) through drinking water and challenge with Clostridium perfringens.” 2007. Web. 18 Jan 2020.

Vancouver:

Tillman GE. Microfloral profile of the broiler midgut intestinal tract and cecum after addition of lupulone (hop β-acid) through drinking water and challenge with Clostridium perfringens. [Internet] [Masters thesis]. University of Georgia; 2007. [cited 2020 Jan 18]. Available from: http://purl.galileo.usg.edu/uga_etd/tillman_glenn_e_200705_ms.

Council of Science Editors:

Tillman GE. Microfloral profile of the broiler midgut intestinal tract and cecum after addition of lupulone (hop β-acid) through drinking water and challenge with Clostridium perfringens. [Masters Thesis]. University of Georgia; 2007. Available from: http://purl.galileo.usg.edu/uga_etd/tillman_glenn_e_200705_ms

University of Georgia

2. Wright, Meredith Suzanne. Evolutionary processes in aquatic bacteria: the transfer and transport of antibiotic resistance in industrially contaminated systems.

Degree: PhD, Ecology, 2007, University of Georgia

URL: http://purl.galileo.usg.edu/uga_etd/wright_meredith_s_200708_phd

► The presence of antibiotic resistant bacteria in non-clinical environments is the result of multiple selective pressures and evolutionary processes. To test the hypothesis that metal… (more)

▼ The presence of antibiotic resistant bacteria in non-clinical environments is the result of multiple selective pressures and evolutionary processes. To test the hypothesis that metal exposure is one selective pressure maintaining antibiotic resistance in aquatic bacteria, both bacterial community tolerance to metals and antibiotics and the relative abundance of antibiotic and metal resistance determinants were quantified along a gradient of metal contamination in freshwater microbial microhabitats on the Savannah River Site (SRS), SC, and in experimental freshwater microcosms. Phenotypic resistance to metals and antibiotics, and resistance determinants were greatest in metal-exposed bacterial communities supporting the hypothesis. The relative abundance of mobile genetic elements called class 1 integrons were then compared in contaminated and reference freshwater and estuarine microhabitats, and in experimental microcosms, to test the hypothesis that elements involved in the acquisition of exogenous sources of DNA are more abundant in bacterial communities exposed to metal contaminants . The structure and predicted function of the integron-associated gene cassette pool was then compared using fragment analysis to assess how metal contamination shapes the gene cassette pool. Results indicate that class 1 integrons are abundant in environmental bacteria, and gene cassettes are a diverse genetic resource that can contribute to bacterial evolution. The complete nucleotide sequence of a 130 kb plasmid from a multidrug resistant Escherichia coli strain isolated from a contaminated estuary was determined to assess potential antibiotic resistance gene flow between clinical and environmental populations and the co-occurrence of metal and antibiotic resistance elements on the same plasmid. The plasmid contained several genes conferring resistance to multiple classes of antibiotics in a region with numerous insertion sequences, transposons, and integrons, yet no known metal resistance genes were identified. The sequence reveals that antibiotic resistance genes prevalent in clinically-derived isolates are prevalent in an environmental strain as well. The results of these studies indicate that antibiotic resistance persists in the environment, and that metal exposure selects for resistance phenotypes, genotypes, and genes involved in horizontal transfer. Advisors/Committee Members: J Vaun McArthur.

Subjects/Keywords: antibiotic resistance

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APA (6^th Edition):

Wright, M. S. (2007). Evolutionary processes in aquatic bacteria: the transfer and transport of antibiotic resistance in industrially contaminated systems. (Doctoral Dissertation). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/wright_meredith_s_200708_phd

Chicago Manual of Style (16^th Edition):

Wright, Meredith Suzanne. “Evolutionary processes in aquatic bacteria: the transfer and transport of antibiotic resistance in industrially contaminated systems.” 2007. Doctoral Dissertation, University of Georgia. Accessed January 18, 2020. http://purl.galileo.usg.edu/uga_etd/wright_meredith_s_200708_phd.

MLA Handbook (7^th Edition):

Wright, Meredith Suzanne. “Evolutionary processes in aquatic bacteria: the transfer and transport of antibiotic resistance in industrially contaminated systems.” 2007. Web. 18 Jan 2020.

Vancouver:

Wright MS. Evolutionary processes in aquatic bacteria: the transfer and transport of antibiotic resistance in industrially contaminated systems. [Internet] [Doctoral dissertation]. University of Georgia; 2007. [cited 2020 Jan 18]. Available from: http://purl.galileo.usg.edu/uga_etd/wright_meredith_s_200708_phd.

Council of Science Editors:

Wright MS. Evolutionary processes in aquatic bacteria: the transfer and transport of antibiotic resistance in industrially contaminated systems. [Doctoral Dissertation]. University of Georgia; 2007. Available from: http://purl.galileo.usg.edu/uga_etd/wright_meredith_s_200708_phd

University of Illinois – Urbana-Champaign

3. Cox, Courtney Lynne. Strategies for thiazole/oxazole-modified microcin discovery.

Degree: PhD, Microbiology, 2015, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/88284

► Natural products continue to be an important source of therapeutically-relevant compounds. With the advent of inexpensive genome sequencing it has become apparent that bacteria produce… (more)

▼ Natural products continue to be an important source of therapeutically-relevant compounds. With the advent of inexpensive genome sequencing it has become apparent that bacteria produce a larger array of natural products than was previously believed. This new wealth in sequence data has potential to be helpful for the discovery of novel compounds by using genome mining. Although strategies of genome mining have become more efficient and capable of identifying novel biosynthetic gene clusters, it remains difficult to correlate gene clusters with natural products. In this dissertation I discuss limitations with the current methods of genome mining and correlating individual natural products with gene clusters. Furthermore, I characterize a rapidly growing family of natural products, the thiazole/oxazole-modified microcins (TOMMs), and discuss novel methods used to correlate the gene clusters to natural products from this family of metabolites. In chapter 2, I establish the sequence diversity and structural capability of bacteria and archaea to produce TOMM natural products. This genome mining characterization was used to identify nine novel classes of TOMMs, including one class from archaeal producers. In chapter 3, I discuss the utilization of genetic techniques to identify and isolate the TOMM natural product from the archaeal species Sulfolobus acidocaldarius. I demonstrate that although genetic manipulation has been previously used for the identification of natural products, comparative metabolomics is difficult to use for routine identification of low-abundance natural products such as the TOMM from S. acidocaldarius. Very few methods have been created to identify natural products from particular gene clusters. Therefore, in chapter 4, I discuss the creation of a novel method for the rapid identification of natural products following bioinformatics prioritization of antibiotic producing strains. This method utilizes the combination of genome mining and the chemical reactivity of natural products to discover new compounds. Dehydrated amino acids are modified residues commonly found in natural products such as TOMMs. I utilize the mild electrophilic chemical reactivity of dehydrated amino acids to label these natural products using a soft nucleophilic probe. These labeled natural products were easily detected using comparative mass spectrometry. Bacterial strains were prioritized by the genome mining established in chapter 2 to reduce the screening time to find a novel natural product. This dissertation presents the addition of novel genome mining and natural product discovery techniques to increase the discovery and production of therapeutically-relevant compounds. Advisors/Committee Members: Mitchell, Douglas A. (advisor), Mitchell, Douglas A (Committee Chair), Whitaker, Rachel J. (committee member), Olsen, Gary J. (committee member), van der Donk, Wilfred A. (committee member).

Subjects/Keywords: antibiotic discovery

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APA (6^th Edition):

Cox, C. L. (2015). Strategies for thiazole/oxazole-modified microcin discovery. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/88284

Chicago Manual of Style (16^th Edition):

Cox, Courtney Lynne. “Strategies for thiazole/oxazole-modified microcin discovery.” 2015. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 18, 2020. http://hdl.handle.net/2142/88284.

MLA Handbook (7^th Edition):

Cox, Courtney Lynne. “Strategies for thiazole/oxazole-modified microcin discovery.” 2015. Web. 18 Jan 2020.

Vancouver:

Cox CL. Strategies for thiazole/oxazole-modified microcin discovery. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2015. [cited 2020 Jan 18]. Available from: http://hdl.handle.net/2142/88284.

Council of Science Editors:

Cox CL. Strategies for thiazole/oxazole-modified microcin discovery. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2015. Available from: http://hdl.handle.net/2142/88284

4. 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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APA (6^th 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 (16^th 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 January 18, 2020. https://repository.library.brown.edu/studio/item/bdr:320579/.

MLA Handbook (7^th Edition):

Durmus, Naside Gozde. “Enhanced Efficacy of Nanotechnology-Driven Approaches against Antibiotic-Resistant Biofilms in the Presence of Metabolites.” 2013. Web. 18 Jan 2020.

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 2020 Jan 18]. 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/

5. 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)

Subjects/Keywords: Antibiotic Resistance

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APA (6^th 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 (16^th Edition):

Vecchione, James J. “Using Chemical, Genetic, and Biochemical Approaches to Understand and Circumvent Antibacterial Drug Resistance.” 2011. Doctoral Dissertation, Brown University. Accessed January 18, 2020. https://repository.library.brown.edu/studio/item/bdr:11186/.

MLA Handbook (7^th Edition):

Vecchione, James J. “Using Chemical, Genetic, and Biochemical Approaches to Understand and Circumvent Antibacterial Drug Resistance.” 2011. Web. 18 Jan 2020.

Vancouver:

Vecchione JJ. Using Chemical, Genetic, and Biochemical Approaches to Understand and Circumvent Antibacterial Drug Resistance. [Internet] [Doctoral dissertation]. Brown University; 2011. [cited 2020 Jan 18]. 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/

University of Debrecen

6. Kristínardóttir, Ester. Comparison of antibiotic consumption in the three internal medicine departments .

Degree: DE – Általános Orvostudományi Kar, 2014, University of Debrecen

URL: http://hdl.handle.net/2437/194847

► Because of the excessive usage of antibiotics, development of resistant bacteria emerges and therefore monitoring of antibiotic resistance and consumption is essential. Data about antibiotic… (more)

Subjects/Keywords: Antibiotic; Comparison

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APA (6^th Edition):

Kristínardóttir, E. (2014). Comparison of antibiotic consumption in the three internal medicine departments . (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/194847

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kristínardóttir, Ester. “Comparison of antibiotic consumption in the three internal medicine departments .” 2014. Thesis, University of Debrecen. Accessed January 18, 2020. http://hdl.handle.net/2437/194847.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kristínardóttir, Ester. “Comparison of antibiotic consumption in the three internal medicine departments .” 2014. Web. 18 Jan 2020.

Vancouver:

Kristínardóttir E. Comparison of antibiotic consumption in the three internal medicine departments . [Internet] [Thesis]. University of Debrecen; 2014. [cited 2020 Jan 18]. Available from: http://hdl.handle.net/2437/194847.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kristínardóttir E. Comparison of antibiotic consumption in the three internal medicine departments . [Thesis]. University of Debrecen; 2014. Available from: http://hdl.handle.net/2437/194847

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Tech

7. 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-Bagchi, Amy Jill (committee member).

Subjects/Keywords: antibiotic; antibiotic resistance gene; dairy calf

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APA (6^th 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 (16^th Edition):

Thames, Callie H. “Excretion of Antibiotic Resistance Genes by Dairy Calves.” 2013. Masters Thesis, Virginia Tech. Accessed January 18, 2020. http://hdl.handle.net/10919/19293.

MLA Handbook (7^th Edition):

Thames, Callie H. “Excretion of Antibiotic Resistance Genes by Dairy Calves.” 2013. Web. 18 Jan 2020.

Vancouver:

Thames CH. Excretion of Antibiotic Resistance Genes by Dairy Calves. [Internet] [Masters thesis]. Virginia Tech; 2013. [cited 2020 Jan 18]. 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

University of Houston

8. Dwibedi, Nilanjana 1979-. Parents’ Expectation to Receive Antibiotic Prescription for Children.

Degree: Pharmacy, College of, 2012, University of Houston

URL: http://hdl.handle.net/10657/503

► Background: The Centers for Disease Control indicated that in 2009, 90 million prescriptions were written for antibiotics in the United States, with half of those… (more)

▼ Background: The Centers for Disease Control indicated that in 2009, 90 million prescriptions were written for antibiotics in the United States, with half of those being "unnecessary or inappropriate". The highest rate of antibiotic use was evident in children younger than 15 years old. Physician’s perception of parents’ expectation to receive antibiotic prescription for their children is a significant predictor of overprescribing antibiotics. Objective: The objective was to manipulate two factors (parents’ ‘perceived benefits of using antibiotics’ and their ‘perceived barriers to visit doctors without any expectation of antibiotic prescription’) and then evaluate whether their level of expectation would change after the manipulation. Methods: A prospective experimental study was conducted using a structured data collection instrument. The purpose of the experiment was to manipulate two variables, perceived barriers and perceived benefits using four scenarios and keep other factors constant. Each subject viewed four situations and expectation associated with each situation was evaluated. Subjects who had at least one child (age ≤ 5 years) during the study and who could speak, read and write English were selected for the study. Data were collected at shopping malls and parks in Houston, TX. Descriptive analyses and repeated measures mixed method covariance adjusted analyses were performed using SAS® 9.3. The a-priori significance level was set as 0.05 for all tests conducted. Results: A total of 300 complete surveys were considered for analyses. The mean age for the sample was 30.36 (± 7.04) years; females represented 55.7% of the sample. The mean general expectation score (before reading any scenario) to receive antibiotic prescription for children was 53.6 (± 25.7). The repeated measure mixed methods analyses indicated that there was 12 point reduction (p < 0.0001) in expectation score after removing perceived barriers from the situational scenarios. Almost 16 point decrease (p < 0.0001) in expectation score was observed after removing perceived benefits from the scenario. There was 18 point decrease (p < 0.0001) in expectation score after removing perceived barriers and perceived benefits from the situational scenario. The study result also indicated that general expectation toward an antibiotic prescription, training in the healthcare field and parents’ preference for communication had significant effect on parents’ expectation. Conclusions: Perceived barriers, perceived benefits alone and in combination have effect on parents’ expectation to receive antibiotic prescription for children. Policy makers as well as intervention programs should consider these factors to enhance successful reduction of antibiotic expectations. Advisors/Committee Members: Sansgiry, Sujit S. (advisor), Johnson, Michael L. (committee member), Essien, Ekere James (committee member), Abughosh, Susan M. (committee member), Mehta, Paras D. (committee member).

Subjects/Keywords: Parents' expectation; antibiotic prescription; antibiotic for children

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APA (6^th Edition):

Dwibedi, N. 1. (2012). Parents’ Expectation to Receive Antibiotic Prescription for Children. (Thesis). University of Houston. Retrieved from http://hdl.handle.net/10657/503

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dwibedi, Nilanjana 1979-. “Parents’ Expectation to Receive Antibiotic Prescription for Children.” 2012. Thesis, University of Houston. Accessed January 18, 2020. http://hdl.handle.net/10657/503.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dwibedi, Nilanjana 1979-. “Parents’ Expectation to Receive Antibiotic Prescription for Children.” 2012. Web. 18 Jan 2020.

Vancouver:

Dwibedi N1. Parents’ Expectation to Receive Antibiotic Prescription for Children. [Internet] [Thesis]. University of Houston; 2012. [cited 2020 Jan 18]. Available from: http://hdl.handle.net/10657/503.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dwibedi N1. Parents’ Expectation to Receive Antibiotic Prescription for Children. [Thesis]. University of Houston; 2012. Available from: http://hdl.handle.net/10657/503

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Waterloo

9. 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 (6^th 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 (16^th Edition):

Scott, Bradley. “Daptomycin: studies on its action mode and on bacterial resistance with model membranes.” 2016. Thesis, University of Waterloo. Accessed January 18, 2020. 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 (7^th Edition):

Scott, Bradley. “Daptomycin: studies on its action mode and on bacterial resistance with model membranes.” 2016. Web. 18 Jan 2020.

Vancouver:

Scott B. Daptomycin: studies on its action mode and on bacterial resistance with model membranes. [Internet] [Thesis]. University of Waterloo; 2016. [cited 2020 Jan 18]. 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

University of Manitoba

10. 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)

Subjects/Keywords: Antibiotic Resistance; Pseudomonas Aeruginosa; Antibiotic Hybrids

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APA (6^th 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 (16^th 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 January 18, 2020. http://hdl.handle.net/1993/32747.

MLA Handbook (7^th 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. 18 Jan 2020.

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 2020 Jan 18]. 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

Texas A&M University

11. Imanpour, Sara. Antibiotic Stewardship in the United States: Antibiotic Over-prescription, Factors Associated with Antibiotic Prescription, and People’s Awareness of Antibiotic Resistance.

Degree: PhD, Health Services Research, 2016, Texas A&M University

URL: http://hdl.handle.net/1969.1/158650

► Antibiotics touch upon almost all aspects of our modern life. They contribute towards increasing life expectancy by reducing the negative outcomes of bacterial infections. Unfortunately,… (more)

▼ Antibiotics touch upon almost all aspects of our modern life. They contribute towards increasing life expectancy by reducing the negative outcomes of bacterial infections. Unfortunately, antibiotics tend to lose their effectiveness over time due to the emergence of antibiotic resistant bacteria. The overuse, misuse, and over-prescription of antibiotics all lead to the development of antibiotic resistant bacteria. This dissertation is a series of three studies that build on each other, each addressing different aspects of the human and organizational factors associated with antibiotic overuse, misuse, and over-prescription in the United States. Study I: The first study focuses on the reasons for antibiotic over-prescription from the point of view of family medicine residents. This qualitative study strives to better understand why medical professional prescribe antibiotics in cases in which antibiotics are not necessary or not useful. The findings suggest that physicians’ behaviors of over-prescribing antibiotics are affected by the organizational conditions within the medical practice including the use of an antibiotic control system and by patients’ expectations. Study II: The second study assesses the potential associations between the duration of visit with a doctor and antibiotic prescriptions for viral infections in outpatient settings. The assessment was done by utilizing National Ambulatory Medical Care Survey data. The results from multivariate logistic regression showed that for every additional minute spent with a physician during an office visit, the mean probability of receiving unnecessary antibiotic prescriptions decreased by 2.4%. Study III: The third is a qualitative study of the general public’s experiences and awareness of antibiotic overuse and antibiotic resistance. Focus groups conducted with twenty people who have traveled into the United States from countries with unrestricted access to antibiotics revealed a paucity of knowledge and awareness of antibiotic resistance and appropriate antibiotic use that must be addressed for any antibiotic stewardship policy to be successful. Despite the very restrictive policies overseeing antibiotic use in the United States, physicians tend to over-prescribe antibiotics and patients often insist on receiving a prescription. The findings of these studies show the need to educate patients through healthcare providers about the consequences of antibiotic overuse and misuse. This would curb the rate of antibiotic overuse, over-prescription, and subsequently, antibiotic resistance. Advisors/Committee Members: McMaughan, Darcy (advisor), Bolin , Jane N (committee member), Morrisey, Michael A (committee member), DeSalvo, Bethany (committee member).

Subjects/Keywords: antibiotic; Health education

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APA (6^th Edition):

Imanpour, S. (2016). Antibiotic Stewardship in the United States: Antibiotic Over-prescription, Factors Associated with Antibiotic Prescription, and People’s Awareness of Antibiotic Resistance. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/158650

Chicago Manual of Style (16^th Edition):

Imanpour, Sara. “Antibiotic Stewardship in the United States: Antibiotic Over-prescription, Factors Associated with Antibiotic Prescription, and People’s Awareness of Antibiotic Resistance.” 2016. Doctoral Dissertation, Texas A&M University. Accessed January 18, 2020. http://hdl.handle.net/1969.1/158650.

MLA Handbook (7^th Edition):

Imanpour, Sara. “Antibiotic Stewardship in the United States: Antibiotic Over-prescription, Factors Associated with Antibiotic Prescription, and People’s Awareness of Antibiotic Resistance.” 2016. Web. 18 Jan 2020.

Vancouver:

Imanpour S. Antibiotic Stewardship in the United States: Antibiotic Over-prescription, Factors Associated with Antibiotic Prescription, and People’s Awareness of Antibiotic Resistance. [Internet] [Doctoral dissertation]. Texas A&M University; 2016. [cited 2020 Jan 18]. Available from: http://hdl.handle.net/1969.1/158650.

Council of Science Editors:

Imanpour S. Antibiotic Stewardship in the United States: Antibiotic Over-prescription, Factors Associated with Antibiotic Prescription, and People’s Awareness of Antibiotic Resistance. [Doctoral Dissertation]. Texas A&M University; 2016. Available from: http://hdl.handle.net/1969.1/158650

McMaster University

12. 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 (6^th 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 (16^th Edition):

Spanogiannopoulos, Peter. “Exploring Rifamycin Inactivation from the Soil Microbiome.” 2014. Doctoral Dissertation, McMaster University. Accessed January 18, 2020. http://hdl.handle.net/11375/16283.

MLA Handbook (7^th Edition):

Spanogiannopoulos, Peter. “Exploring Rifamycin Inactivation from the Soil Microbiome.” 2014. Web. 18 Jan 2020.

Vancouver:

Spanogiannopoulos P. Exploring Rifamycin Inactivation from the Soil Microbiome. [Internet] [Doctoral dissertation]. McMaster University; 2014. [cited 2020 Jan 18]. 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

University of Waterloo

13. Muraih, Jawad K. Mode of Action of Daptomycin, a Lipopeptide Antibiotic.

Degree: 2013, University of Waterloo

URL: http://hdl.handle.net/10012/7323

► Daptomycin is a lipopeptide antibiotic that contains 13 amino acids and an N-terminally attached fatty acyl residue. The antibiotic kills Gram-positive bacteria by membrane depolarization.… (more)

▼ Daptomycin is a lipopeptide antibiotic that contains 13 amino acids and an N-terminally attached fatty acyl residue. The antibiotic kills Gram-positive bacteria by membrane depolarization. It has long been assumed that the mode of action of daptomycin involves the formation of oligomers on the bacterial cell membrane; however, at the outset of my studies, this had not been experimentally demonstrated. In the work described in this thesis, I have used fluorescence energy transfer (FRET) between native daptomycin and an NBD-labeled daptomycin derivative to demonstrate that the antibiotic indeed forms oligomers on bacterial cell membranes. In a liposome model, oligomer formation depends on calcium and on phosphatidylglycerol (PG). The oligomer forms rapidly and is stable for a length of time longer than required for the bactericidal effect. Through variation of the ratio of FRET donor (native daptomycin) and acceptor (NBD-daptomycin), I have determined that the oligomer consists of approximately 6–7 molecules, or, depending on the structure of the oligomer, possibly up to twice that number. Oligomer formation on liposomes and on bacterial membranes was confirmed using excimer fluorescence of a perylene-labeled daptomycin derivative. Excimer fluorescence was also used to demonstrate a stoichiometric interaction between daptomycin and PG. It has previously been shown that the bactericidal activity of daptomycin requires calcium and correlates with the concentration of PG in the bacterial cell membrane; these requirements mirror those observed here for oligomer formation. Furthermore, membrane permeabilization is selective, and electron microscopy of bacterial membranes exposed to daptomycin has revealed no discontinuities or accretions of electron density. Both of these findings suggest formation of a small membrane lesion, which is compatible with the small size of the oligomer that was determined here. In conjunction with these previous findings, the experiments contained in my thesis strongly suggest that the oligomer is the bactericidal form of daptomycin.

Subjects/Keywords: Daptomycin; Oligomerization; Antibiotic

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APA (6^th Edition):

Muraih, J. K. (2013). Mode of Action of Daptomycin, a Lipopeptide Antibiotic. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/7323

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Muraih, Jawad K. “Mode of Action of Daptomycin, a Lipopeptide Antibiotic.” 2013. Thesis, University of Waterloo. Accessed January 18, 2020. http://hdl.handle.net/10012/7323.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Muraih, Jawad K. “Mode of Action of Daptomycin, a Lipopeptide Antibiotic.” 2013. Web. 18 Jan 2020.

Vancouver:

Muraih JK. Mode of Action of Daptomycin, a Lipopeptide Antibiotic. [Internet] [Thesis]. University of Waterloo; 2013. [cited 2020 Jan 18]. Available from: http://hdl.handle.net/10012/7323.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Muraih JK. Mode of Action of Daptomycin, a Lipopeptide Antibiotic. [Thesis]. University of Waterloo; 2013. Available from: http://hdl.handle.net/10012/7323

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Arizona State University

14. Weeks, Jon W. Genetics of Functional AcrAB-TolC Tripartite Complex Assembly.

Degree: PhD, Microbiology, 2012, Arizona State University

URL: http://repository.asu.edu/items/15167

► Intrinsic antibiotic resistance is of growing concern in modern medical treatment. The primary action of multidrug resistant strains is through over-expression of active transporters which… (more)

▼ Intrinsic antibiotic resistance is of growing concern in modern medical treatment. The primary action of multidrug resistant strains is through over-expression of active transporters which recognize a broad range of antibiotics. In Escherichia coli, the TolC-AcrAB complex has become a model system to understand antibiotic efflux. While the structures of these three proteins (and many of their homologs) are known, the exact mechanisms of interaction are still poorly understood. By mutational analysis of the TolC turn 1 residues, a drug hypersensitive mutant has been identified which is defective in functional interactions with AcrA and AcrB. Antibiotic resistant revertants carry alterations in both TolC and AcrA act by stabilizing functional complex assembly and opening of the TolC aperture, as monitored by stability of a labile TolC mutant and sensitivity to vancomycin, respectively. Alterations in the AcrB periplasmic hairpin loops lead to a similar antibiotic hypersensitivity phenotype and destabilized complex assembly. Likewise, alterations in TolC which constitutively open the aperture suppress this antibiotic sensitivity. Suppressor alterations in AcrA and AcrB partially restore antibiotic resistance by mediating stability of the complex. The AcrA suppressor alterations isolated in these studies map to the three crystallized domains and it is concluded they alter the AcrA conformation such that it is permanently fixed in an active state, which wild type only transiently goes through when activated by AcrB. Through this genetic evidence, a direct interaction between TolC and AcrB which is stabilized by AcrA has been proposed. In addition to stabilizing the interactions between TolC and AcrB, AcrA is also responsible for triggering opening of the TolC aperture by mediating energy flow from AcrB to TolC. By permanently altering the conformation of AcrA, suppressor mutants allow defective TolC or AcrB mutants to regain functional interactions lost by the initial mutations. The data provide the genetic proof for direct interaction between AcrB and that AcrA mediated opening of TolC requires AcrB as a scaffold.

Subjects/Keywords: Microbiology; Antibiotic Efflux

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APA (6^th Edition):

Weeks, J. W. (2012). Genetics of Functional AcrAB-TolC Tripartite Complex Assembly. (Doctoral Dissertation). Arizona State University. Retrieved from http://repository.asu.edu/items/15167

Chicago Manual of Style (16^th Edition):

Weeks, Jon W. “Genetics of Functional AcrAB-TolC Tripartite Complex Assembly.” 2012. Doctoral Dissertation, Arizona State University. Accessed January 18, 2020. http://repository.asu.edu/items/15167.

MLA Handbook (7^th Edition):

Weeks, Jon W. “Genetics of Functional AcrAB-TolC Tripartite Complex Assembly.” 2012. Web. 18 Jan 2020.

Vancouver:

Weeks JW. Genetics of Functional AcrAB-TolC Tripartite Complex Assembly. [Internet] [Doctoral dissertation]. Arizona State University; 2012. [cited 2020 Jan 18]. Available from: http://repository.asu.edu/items/15167.

Council of Science Editors:

Weeks JW. Genetics of Functional AcrAB-TolC Tripartite Complex Assembly. [Doctoral Dissertation]. Arizona State University; 2012. Available from: http://repository.asu.edu/items/15167

15. 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)

Subjects/Keywords: Antibiotic resistance; Bangladesh

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APA (6^th 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 (16^th Edition):

Rashid, Muhammad Mahmudur. “Antibiotic resistance in different ecological niches in Bangladesh.” 2013. Thesis, Umeå University. Accessed January 18, 2020. 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 (7^th Edition):

Rashid, Muhammad Mahmudur. “Antibiotic resistance in different ecological niches in Bangladesh.” 2013. Web. 18 Jan 2020.

Vancouver:

Rashid MM. Antibiotic resistance in different ecological niches in Bangladesh. [Internet] [Thesis]. Umeå University; 2013. [cited 2020 Jan 18]. 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

Virginia Tech

16. Riquelme Breazeal, Maria Virginia. Improved monitoring of emerging environmental biocontaminants through (nano)biosensors and molecular analyses.

Degree: PhD, Civil and Environmental Engineering, 2016, Virginia Tech

URL: http://hdl.handle.net/10919/83419

► Outputs of human-derived chemicals and constituents to the environment, and shifts in these outputs, can result in unintended consequences to human and ecological health. One… (more)

▼ Outputs of human-derived chemicals and constituents to the environment, and shifts in these outputs, can result in unintended consequences to human and ecological health. One such shift is the advent of the modern antibiotic era, in which mass production and outputs of antibiotics, which are mostly naturally-derived microbial defense compounds and include a few synthetic antimicrobials, has profound implications for contributing to the spread of antibiotic resistance. Antibiotic resistance arises from mutations and/or sharing of antibiotic resistance genes (ARGs) among bacteria via horizontal gene transfer, with carriage of ARGs by pathogenic bacteria of particular concern to human health. While most attention to stopping the spread of antibiotic resistance has been devoted to the clinic, it is critical to consider the environmental origin, ecology and pathways by which antibiotic resistance spreads in order to develop comprehensive strategies to combat antibiotic resistance. In particular, wastewater treatment plants (WWTPs) represent a potentially key critical control point given that they receive antibiotic resistant bacteria (ARB) and ARGs from the population, which are then routed to activated sludge biological treatment, consisting of high density, highly active microbial populations. The research projects described in this dissertation aimed to explore the occurrence of ARGs in WWTPs, particularly WWTPs in developing countries representing the extremes of what is expected to be encountered in terms of potential to spread antibiotic resistance, and to improve and apply novel technologies for monitoring key markers of antibiotic resistance in WWTPs and affected environments. The pathogen Staphylococcus aureus and a corresponding ARG (methicillin resistance mecA gene) were chosen as model biocontaminants of concern due to their environmental and public health relevance. The results reported in Chapters 3-5 advance the knowledge of bio(nano)sensing techniques and highlight areas of promise and challenge. The results reported in Chapter 2 provided insight into the baseline levels of ARGs expected in a highly impacted WWTP in India, thereby highlighting the magnitude and global scale of the problem of antibiotic resistance as well as the need for innovative solutions. Advisors/Committee Members: Pruden-Bagchi, Amy Jill (committeechair), Vikesland, Peter J. (committeechair), Hochella, Michael F. Jr. (committee member), Agah, Masoud (committee member).

Subjects/Keywords: Nanosensors; biosensors; antibiotic resistance; antibiotic resistance genes; ARGs; antibiotic resistant bacteria; ARB

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APA (6^th Edition):

Riquelme Breazeal, M. V. (2016). Improved monitoring of emerging environmental biocontaminants through (nano)biosensors and molecular analyses. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/83419

Chicago Manual of Style (16^th Edition):

Riquelme Breazeal, Maria Virginia. “Improved monitoring of emerging environmental biocontaminants through (nano)biosensors and molecular analyses.” 2016. Doctoral Dissertation, Virginia Tech. Accessed January 18, 2020. http://hdl.handle.net/10919/83419.

MLA Handbook (7^th Edition):

Riquelme Breazeal, Maria Virginia. “Improved monitoring of emerging environmental biocontaminants through (nano)biosensors and molecular analyses.” 2016. Web. 18 Jan 2020.

Vancouver:

Riquelme Breazeal MV. Improved monitoring of emerging environmental biocontaminants through (nano)biosensors and molecular analyses. [Internet] [Doctoral dissertation]. Virginia Tech; 2016. [cited 2020 Jan 18]. Available from: http://hdl.handle.net/10919/83419.

Council of Science Editors:

Riquelme Breazeal MV. Improved monitoring of emerging environmental biocontaminants through (nano)biosensors and molecular analyses. [Doctoral Dissertation]. Virginia Tech; 2016. Available from: http://hdl.handle.net/10919/83419

University of Georgia

17. Smith, Jacinta L. Integron and tetracycline determinant carriage among strains of commensal Esherichia coli isolated from broiler chickens.

Degree: MS, Medical Microbiology, 2004, University of Georgia

URL: http://purl.galileo.usg.edu/uga_etd/smith_jacinta_l_200405_ms

► Some authorities question the use of antimicrobials in food production based on data that suggests usage may lead to an increase in multiple drug resistance… (more)

Subjects/Keywords: Antibiotic resistance

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APA (6^th Edition):

Smith, J. L. (2004). Integron and tetracycline determinant carriage among strains of commensal Esherichia coli isolated from broiler chickens. (Masters Thesis). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/smith_jacinta_l_200405_ms

Chicago Manual of Style (16^th Edition):

Smith, Jacinta L. “Integron and tetracycline determinant carriage among strains of commensal Esherichia coli isolated from broiler chickens.” 2004. Masters Thesis, University of Georgia. Accessed January 18, 2020. http://purl.galileo.usg.edu/uga_etd/smith_jacinta_l_200405_ms.

MLA Handbook (7^th Edition):

Smith, Jacinta L. “Integron and tetracycline determinant carriage among strains of commensal Esherichia coli isolated from broiler chickens.” 2004. Web. 18 Jan 2020.

Vancouver:

Smith JL. Integron and tetracycline determinant carriage among strains of commensal Esherichia coli isolated from broiler chickens. [Internet] [Masters thesis]. University of Georgia; 2004. [cited 2020 Jan 18]. Available from: http://purl.galileo.usg.edu/uga_etd/smith_jacinta_l_200405_ms.

Council of Science Editors:

Smith JL. Integron and tetracycline determinant carriage among strains of commensal Esherichia coli isolated from broiler chickens. [Masters Thesis]. University of Georgia; 2004. Available from: http://purl.galileo.usg.edu/uga_etd/smith_jacinta_l_200405_ms

18. Kleinman, Brian. In Vitro Comparison of the Push-Out Bond Strength of Three Endodontic Sealers With and Without Amoxicillin.

Degree: 2011, Marquette University

URL: https://epublications.marquette.edu/theses_open/76

► INTRODUCTION: The purpose of this in vitro study was to compare the push-out bond strengths of three endodontic sealers with and without amoxicillin. METHODS: Thirty… (more)

Subjects/Keywords: Antibiotic; Bond strength; Endodontics; Sealers

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APA (6^th Edition):

Kleinman, B. (2011). In Vitro Comparison of the Push-Out Bond Strength of Three Endodontic Sealers With and Without Amoxicillin. (Thesis). Marquette University. Retrieved from https://epublications.marquette.edu/theses_open/76

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kleinman, Brian. “In Vitro Comparison of the Push-Out Bond Strength of Three Endodontic Sealers With and Without Amoxicillin.” 2011. Thesis, Marquette University. Accessed January 18, 2020. https://epublications.marquette.edu/theses_open/76.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kleinman, Brian. “In Vitro Comparison of the Push-Out Bond Strength of Three Endodontic Sealers With and Without Amoxicillin.” 2011. Web. 18 Jan 2020.

Vancouver:

Kleinman B. In Vitro Comparison of the Push-Out Bond Strength of Three Endodontic Sealers With and Without Amoxicillin. [Internet] [Thesis]. Marquette University; 2011. [cited 2020 Jan 18]. Available from: https://epublications.marquette.edu/theses_open/76.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kleinman B. In Vitro Comparison of the Push-Out Bond Strength of Three Endodontic Sealers With and Without Amoxicillin. [Thesis]. Marquette University; 2011. Available from: https://epublications.marquette.edu/theses_open/76

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Minnesota

19. 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 (6^th 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 (16^th Edition):

Lang, Kevin. “Transcriptional regulation of incompatibility type A/C plasmids.” 2015. Doctoral Dissertation, University of Minnesota. Accessed January 18, 2020. http://hdl.handle.net/11299/174866.

MLA Handbook (7^th Edition):

Lang, Kevin. “Transcriptional regulation of incompatibility type A/C plasmids.” 2015. Web. 18 Jan 2020.

Vancouver:

Lang K. Transcriptional regulation of incompatibility type A/C plasmids. [Internet] [Doctoral dissertation]. University of Minnesota; 2015. [cited 2020 Jan 18]. 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

University of Illinois – Urbana-Champaign

20. 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 (6^th 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 (16^th Edition):

Garg, Neha. “Exploring and understanding lantibiotic biosynthesis.” 2014. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 18, 2020. http://hdl.handle.net/2142/46883.

MLA Handbook (7^th Edition):

Garg, Neha. “Exploring and understanding lantibiotic biosynthesis.” 2014. Web. 18 Jan 2020.

Vancouver:

Garg N. Exploring and understanding lantibiotic biosynthesis. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2014. [cited 2020 Jan 18]. 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 Illinois – Urbana-Champaign

21. Endo, Matthew Masashi. Synthesis-enabled understanding of the mechanism of action of amphotericin B and the development of increased therapeutic derivatives.

Degree: MS, Chemistry, 2016, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/92874

► The polyene macrolide amphotericin B (AmB) remains a critically vital antifungal as the last line of defense against a wide range of life-threatening fungal pathogen.… (more)

▼ The polyene macrolide amphotericin B (AmB) remains a critically vital antifungal as the last line of defense against a wide range of life-threatening fungal pathogen. Despite its clinical usage for over half a century, AmB has evaded the development of clinically relevant microbial resistance. AmB has been shown to form ion channels similar to that of their protein counterparts, which has led to the proposal that AmB kills yeast cells via membrane permeabilization. The capacity for ion channel formation and cytotoxicity of AmB are thought to be dependent upon membranous sterol, but the role of sterols in this mechanism and whether membrane permeabilizaton and biological activity are even linked has remained unclear. Thus, the complete understanding of the mechanism of action of AmB would enable the development of new antifungals with an improved therapeutic index, as well as guide the pursuit of new antimicrobials that evade resistance. To elucidate the operative mechanism, we pursued a systematic functional group deletion strategy where derivatives of AmB are synthesized lacking a single protic functional group to understand its role in AmB’s activity. The C35 hydroxyl group of AmB has been proposed to be critical for ion channel formation and so we accessed the derivative lacking the C35 hydroxyl via an iterative cross-coupling (ICC) strategy. The resulting derivative maintained the capacity to bind membranous ergosterol, but could no longer cause membrane permeabilization. Despite the lack of channel activity, this derivative still demonstrated potent fungicidal activity. Deletion of the mycosamine sugar yielded a derivative that could no longer bind ergosterol and was completely inactive against yeast. Collectively, these results led us to conclude that the primary mechanism by which AmB kills yeast is the binding of the ergosterol and that channel formation is a complementary mechanism that marginally increases AmB's potency. This finding suggests that toxicity to humans is likely due to the binding of the major mammalian sterol: cholesterol. Given the importance of the mycosamine appendage on the binding of sterol, we pursued an atomistic understanding of this interaction. The axial C2' hydroxyl group of AmB has been proposed to be critical in binding both sterols. Surprisingly, derivatives lacking or epimerizing the C2' hydroxyl maintained the capacity to bind ergosterol but could no longer bind cholesterol. Consistent with sterol binding being the operative mechanism for toxicity, both derivatives exhibited potent antifungal activity but no toxicity in human cells and mice. However, synthetic access to both derivatives limited their further pursuit. We hypothesized that the sterol selectivity resulted from a ligand-selective allosteric modification and proposed that a similar effect could be achieved by derivatization of the accessible C41 carboxylate. Similar to the C2' modified analogues, the new AmB ureas also demonstrated a preferential binding for ergosterol over cholesterol. This corresponded with… Advisors/Committee Members: Burke, Martin D (advisor).

Subjects/Keywords: antifungal; antibiotic; synthesis; amphotericin B

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APA (6^th Edition):

Endo, M. M. (2016). Synthesis-enabled understanding of the mechanism of action of amphotericin B and the development of increased therapeutic derivatives. (Thesis). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/92874

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Endo, Matthew Masashi. “Synthesis-enabled understanding of the mechanism of action of amphotericin B and the development of increased therapeutic derivatives.” 2016. Thesis, University of Illinois – Urbana-Champaign. Accessed January 18, 2020. http://hdl.handle.net/2142/92874.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Endo, Matthew Masashi. “Synthesis-enabled understanding of the mechanism of action of amphotericin B and the development of increased therapeutic derivatives.” 2016. Web. 18 Jan 2020.

Vancouver:

Endo MM. Synthesis-enabled understanding of the mechanism of action of amphotericin B and the development of increased therapeutic derivatives. [Internet] [Thesis]. University of Illinois – Urbana-Champaign; 2016. [cited 2020 Jan 18]. Available from: http://hdl.handle.net/2142/92874.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Endo MM. Synthesis-enabled understanding of the mechanism of action of amphotericin B and the development of increased therapeutic derivatives. [Thesis]. University of Illinois – Urbana-Champaign; 2016. Available from: http://hdl.handle.net/2142/92874

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign

22. Circello, Benjamin T. Investigations into the biosynthesis and mode of action of the phosphonate antibiotic dehydrophos.

Degree: PhD, 0322, 2011, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/18576

► Dehydrophos is a vinyl phosphonate tripeptide produced by Streptomyces luridus with demonstrated broad spectrum antibiotic activity. Dehydrophos antibiotic activity was determined to be dependent on… (more)

Subjects/Keywords: phosphonate; antibiotic; Streptomyces; drug discovery

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Circello, B. T. (2011). Investigations into the biosynthesis and mode of action of the phosphonate antibiotic dehydrophos. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/18576

Chicago Manual of Style (16^th Edition):

Circello, Benjamin T. “Investigations into the biosynthesis and mode of action of the phosphonate antibiotic dehydrophos.” 2011. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 18, 2020. http://hdl.handle.net/2142/18576.

MLA Handbook (7^th Edition):

Circello, Benjamin T. “Investigations into the biosynthesis and mode of action of the phosphonate antibiotic dehydrophos.” 2011. Web. 18 Jan 2020.

Vancouver:

Circello BT. Investigations into the biosynthesis and mode of action of the phosphonate antibiotic dehydrophos. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2011. [cited 2020 Jan 18]. Available from: http://hdl.handle.net/2142/18576.

Council of Science Editors:

Circello BT. Investigations into the biosynthesis and mode of action of the phosphonate antibiotic dehydrophos. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/18576

University of Notre Dame

23. Leslie Danette Patterson. Syntheses of Desferrioxamine B Conjugates for Use in Antibiotic Delivery and Iron Overload Diseases</h1>.

Degree: PhD, Chemistry and Biochemistry, 2010, University of Notre Dame

URL: https://curate.nd.edu/show/df65v694z35

► Many complex siderophore conjugates have been synthesized by the Miller group and others for the purpose of antibiotic delivery, the treatment of iron overload… (more)

▼ Many complex siderophore conjugates have been synthesized by the Miller group and others for the purpose of antibiotic delivery, the treatment of iron overload diseases and for the use of MRI contrast agents. Desferrioxamine B (DFO), a commercially available siderophore, has rarely been used to synthesize such conjugates due to the complexity of starting from a complete, non-protected siderophore. The methodology needed to allow DFO conjugates to be easily prepared without the need for standard protecting groups has been discussed here. A DFO-ferritin binding peptide conjugate was synthesized by using Fe(III) as a protecting group. Using a pH controlled EDC coupling reaction, selective reaction at the terminal serine of the ferritin binding peptide versus the internal lysine of the peptide was facilitated. The DFO-peptide conjugate was found to increase the demineralization of ferritin by 8-times. After the synthesis of the first peptide conjugate a scaled up synthesis was designed to provide enough conjugate for in vivo testing in mice. A maleimide linker containing DFO derivative was synthesized. A second DFO-ferritin binding peptide conjugate was synthesized using a thiol maleimide Michael reaction as the key conjugation step. Preliminary results indicate the DFO-peptide conjugate does not increase iron excretion. A DFO-dual action cephalosporin conjugated was designed which would also use a thiol maleimide Michael reaction for the key conjugation step. A dual action cephalosporin (DAC) releases a drug when attacked at the Ìøå¢-lactam ring. Although the final conjugation step had been worked out, the synthesis of the cephalosporin portion of the DFO-DAC conjugate had not. Work toward the cephalosporin portion of the conjugate led to the development of a method to deacetylate an acid protected cephalosporin. The final DFO-DAC conjugate was not obtained due to the inability to remove the cephalosporin protecting groups. Further development of the methodology reported, however, is anticipated to provide an opportunity for the discovery of new, selective antibiotics and diagnostic agents. Advisors/Committee Members: Marvin J. Miller, Committee Chair.

Subjects/Keywords: antibiotic; cephalosporin; siderophore; iron overload

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APA (6^th Edition):

Patterson, L. D. (2010). Syntheses of Desferrioxamine B Conjugates for Use in Antibiotic Delivery and Iron Overload Diseases</h1>. (Doctoral Dissertation). University of Notre Dame. Retrieved from https://curate.nd.edu/show/df65v694z35

Chicago Manual of Style (16^th Edition):

Patterson, Leslie Danette. “Syntheses of Desferrioxamine B Conjugates for Use in Antibiotic Delivery and Iron Overload Diseases</h1>.” 2010. Doctoral Dissertation, University of Notre Dame. Accessed January 18, 2020. https://curate.nd.edu/show/df65v694z35.

MLA Handbook (7^th Edition):

Patterson, Leslie Danette. “Syntheses of Desferrioxamine B Conjugates for Use in Antibiotic Delivery and Iron Overload Diseases</h1>.” 2010. Web. 18 Jan 2020.

Vancouver:

Patterson LD. Syntheses of Desferrioxamine B Conjugates for Use in Antibiotic Delivery and Iron Overload Diseases</h1>. [Internet] [Doctoral dissertation]. University of Notre Dame; 2010. [cited 2020 Jan 18]. Available from: https://curate.nd.edu/show/df65v694z35.

Council of Science Editors:

Patterson LD. Syntheses of Desferrioxamine B Conjugates for Use in Antibiotic Delivery and Iron Overload Diseases</h1>. [Doctoral Dissertation]. University of Notre Dame; 2010. Available from: https://curate.nd.edu/show/df65v694z35

Addis Ababa University

24. Getnet, Worku. Isolation and Antibiotic Susceptibility of Shigella and Campylobacter from Acute Enteric Infections in Yekatit 12 Hospital and Shiromeda Health center, Addis Ababa .

Degree: 2012, Addis Ababa University

URL: http://etd.aau.edu.et/dspace/handle/123456789/2931

► Background -Acute infective diarrhoea and gastroenteritis are major causes of ill health and premature death in developing world due, in large part, to the lack… (more)

▼ Background -Acute infective diarrhoea and gastroenteritis are major causes of ill health and premature death in developing world due, in large part, to the lack of safe drinking water, sanitation and hygiene, as well as poorer overall health and nutritional status. Among the leading causes of infectious diarrhoea, Campylobacter and Shigella contribute a lot. Antimicrobial resistance has developed among many of the major diarrheal bacterial pathogens and complicated the selection of antibiotics for the treatment of enteric bacterial pathogens, particularly to commonly used antimicrobial agents such as ampicillin, tetracycline and trimethoprim–sulfamethoxazole. Objective - To isolate and determine antibiotic susceptibility pattern of Shigella, and Campylobacter from acute enteric infections in Addis Ababa Method - A cross sectional study was conducted from December 2010 to March 2011 at Shiromeda health center (n=254) and Yekatit 12 Hospital (n=140). All diarrheal stool specimens were cultured for isolation of Shigella and Campylobacter species. Antimicrobial susceptibility testing was performed for culture isolates according to the method of Clinical and Laboratory Standards Institute (CLSI) by disk diffusion method. Result – A total of 163 enteropathogens were isolated from 394 patients that had acute diarrhea. The isolates were 37 (9.4%) Shigella species, 19 (4.8%) Campylobacter species, 23 (5.8%) Salmonella species and 84 (21.3%) parasites. 192 (48.7%) of the patients were females and 202 (51.3%) were males making the female to male ratio 1:1.05. The antimicrobial susceptibility pattern for 37 strains of Shigella isolates showed 67.6% resistance to ampicillin followed by, trimethoprim-sulfamethoxazole (64.7%), and chloramphenicol (40.5%). More than 90% of the strains were sensitive to nalidixic acid ciprofloxacin, norfloxacin and polymyxin B. Multiple resistances (resistant to two or more drugs) were observed in 23 (62.1%) of the isolates. All Campylobacter spp. were susceptible to chloramphenicol and showed low resistance rates (<60%) against, trimethoprim-sulfamethoxazole, ampicillin, nalidixic acid, ciprofloxacin and erythromycin. Conclusion- the results of the present study showed the high prevalence for Shigella spp. while Campylobacter spp. showed a moderate one. Continuous surveillance of the prevalence and VIII antibiotic susceptibility pattern of diarrheal bacteria in hospitals and in the community is needed which should be the basis for empiric therapy. Advisors/Committee Members: Ato Tamrat Abebe (PhD candidate, Department of Microbiology, Immunology & Parasitology Addis Ababa University ) (advisor).

Subjects/Keywords: Antibiotic Susceptibility; Acute Enteric Infections

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Getnet, W. (2012). Isolation and Antibiotic Susceptibility of Shigella and Campylobacter from Acute Enteric Infections in Yekatit 12 Hospital and Shiromeda Health center, Addis Ababa . (Thesis). Addis Ababa University. Retrieved from http://etd.aau.edu.et/dspace/handle/123456789/2931

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Getnet, Worku. “Isolation and Antibiotic Susceptibility of Shigella and Campylobacter from Acute Enteric Infections in Yekatit 12 Hospital and Shiromeda Health center, Addis Ababa .” 2012. Thesis, Addis Ababa University. Accessed January 18, 2020. http://etd.aau.edu.et/dspace/handle/123456789/2931.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Getnet, Worku. “Isolation and Antibiotic Susceptibility of Shigella and Campylobacter from Acute Enteric Infections in Yekatit 12 Hospital and Shiromeda Health center, Addis Ababa .” 2012. Web. 18 Jan 2020.

Vancouver:

Getnet W. Isolation and Antibiotic Susceptibility of Shigella and Campylobacter from Acute Enteric Infections in Yekatit 12 Hospital and Shiromeda Health center, Addis Ababa . [Internet] [Thesis]. Addis Ababa University; 2012. [cited 2020 Jan 18]. Available from: http://etd.aau.edu.et/dspace/handle/123456789/2931.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Getnet W. Isolation and Antibiotic Susceptibility of Shigella and Campylobacter from Acute Enteric Infections in Yekatit 12 Hospital and Shiromeda Health center, Addis Ababa . [Thesis]. Addis Ababa University; 2012. Available from: http://etd.aau.edu.et/dspace/handle/123456789/2931

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

The Ohio State University

25. Tumin, Rachel Ann. Social and healthcare factors of methicillin-resistant <i>Staphylococcus aureus</i> resistance to targeted antibiotics.

Degree: MS, Public Health, 2011, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1311691184

► Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a significant cause of healthcare- and community-acquired infections. The emergence and spread of MRSA strains resistant to commonly prescribed antibiotics… (more)

Subjects/Keywords: Epidemiology; MRSA; antibiotic resistance

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APA (6^th Edition):

Tumin, R. A. (2011). Social and healthcare factors of methicillin-resistant <i>Staphylococcus aureus</i> resistance to targeted antibiotics. (Masters Thesis). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1311691184

Chicago Manual of Style (16^th Edition):

Tumin, Rachel Ann. “Social and healthcare factors of methicillin-resistant <i>Staphylococcus aureus</i> resistance to targeted antibiotics.” 2011. Masters Thesis, The Ohio State University. Accessed January 18, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1311691184.

MLA Handbook (7^th Edition):

Tumin, Rachel Ann. “Social and healthcare factors of methicillin-resistant <i>Staphylococcus aureus</i> resistance to targeted antibiotics.” 2011. Web. 18 Jan 2020.

Vancouver:

Tumin RA. Social and healthcare factors of methicillin-resistant <i>Staphylococcus aureus</i> resistance to targeted antibiotics. [Internet] [Masters thesis]. The Ohio State University; 2011. [cited 2020 Jan 18]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1311691184.

Council of Science Editors:

Tumin RA. Social and healthcare factors of methicillin-resistant <i>Staphylococcus aureus</i> resistance to targeted antibiotics. [Masters Thesis]. The Ohio State University; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1311691184

Technical University of Lisbon

26. Monchique, Cláudia Raquel Oliveira. Evolução da resistência aos antibióticos em Staphylococcus spp. : 1999 a 2006.

Degree: 2013, Technical University of Lisbon

URL: http://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/6229

►

Dissertação de Mestrado Integrado em Medicina Veterinária

O género Staphylococcus tem importância a nível clínico e económico, sendo que a emergência de estirpes meticilina resistente… (more)

▼

Dissertação de Mestrado Integrado em Medicina Veterinária

O género Staphylococcus tem importância a nível clínico e económico, sendo que a emergência de estirpes meticilina resistente e multirresistentes tornam-no num assunto atual em Medicina Humana e Veterinária. As 383 amostras de infeções clínicas analisadas foram recebidas pelo Laboratório de Análises Clínicas da FMV-UL ao longo de um período de 8 anos (1999-2006). O teste de susceptibilidade aos antibióticos foi realizado por difusão de disco usando 37 antibióticos. As espécies de estafilococos foram identificadas por amplificação por PCR dos respetivos genes nuc. Os genes mecA e mecC foram pesquisados por PCR. No total, 293 isolados foram resistentes a pelo menos um antibiótico (76,50%), com as maiores frequências de resistência à penicilina e ampicilina (53%). A maior percentagem de resistência a um antibiótico verificou-se em S. pseudintermedius (80,84%), seguido dos S. aureus (75%), estafilococos coagulase-negativo (ECN) (68,18%) e S. schleiferi (63,44%). Globalmente, 132 isolados foram multirresistentes (34,36%) e apenas 23,50% dos isolados foram suscetíveis a todos os antibióticos testados. A resistência aumentou com o tempo, sendo 2004 o ano com maior percentagem de isolados resistentes de estafilococos (85%). Dez isolados eram resistentes à oxacilina, mas só oito eram mecA positivo (sete ECN e um S. aureus) e nenhum foi positivo para o mecC. Os nossos resultados confirmam a elevada resistência aos antibióticos em estafilococos e ressaltam a importância de uma monitorização contínua dos padrões de resistência para ajustamento da estratégia antimicrobiana.

ABSTRACT - Evolution in antibiotics resistance in Staphylococcus spp. – 1999 a 2006 - The genus Staphylococcus has importance at clinical and economic level, with the emergence of methicillin-resistant and multiresistant strains making it a current issue in Human and Veterinary Medicine. The 383 clinical samples analyzed were received by the Laboratory of Clinical Analysis of the FMV-UL over a period of 8 years (1999-2006). The antimicrobial susceptibility testing was performed by disk diffusion using 37 antibiotics. Staphylococcal species were identified by PCR amplification of the respective nuc gene. The mecA and mecC genes were screened by PCR. In total, 293 isolates were resistant to at least one antibiotic (76,50%), with higher frequencies of resistance to penicillin and ampicillin (53%). The highest resistance to one antibiotic was found in S. pseudintermedius (80,84%) followed by S. aureus (75%), coagulase-negative staphylococci (CNS) (68,18%) and S. schleiferi (63,44%). Overall, 132 isolates were multidrug resistant (34,46%) and only 23,50% of the isolates were susceptible to all the antibiotics tested. Resistance increased over time, with the highest level observed in 2004 (85%). Ten isolates were resistant to oxacilin, but only 8 were mecA-positive (seven CNS and one S. aureus) and none was mecC-positive. Our results confirmed that antimicrobial resistance is very frequent in…

Advisors/Committee Members: Pomba, Maria Constança Matias Ferreira, Félix, Nuno Manuel Mira Flor Santos.

Subjects/Keywords: Staphylococcus; resistências; antibióticos; resistances; antibiotic

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Monchique, C. R. O. (2013). Evolução da resistência aos antibióticos em Staphylococcus spp. : 1999 a 2006. (Thesis). Technical University of Lisbon. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/6229

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Monchique, Cláudia Raquel Oliveira. “Evolução da resistência aos antibióticos em Staphylococcus spp. : 1999 a 2006.” 2013. Thesis, Technical University of Lisbon. Accessed January 18, 2020. http://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/6229.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Monchique, Cláudia Raquel Oliveira. “Evolução da resistência aos antibióticos em Staphylococcus spp. : 1999 a 2006.” 2013. Web. 18 Jan 2020.

Vancouver:

Monchique CRO. Evolução da resistência aos antibióticos em Staphylococcus spp. : 1999 a 2006. [Internet] [Thesis]. Technical University of Lisbon; 2013. [cited 2020 Jan 18]. Available from: http://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/6229.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Monchique CRO. Evolução da resistência aos antibióticos em Staphylococcus spp. : 1999 a 2006. [Thesis]. Technical University of Lisbon; 2013. Available from: http://www.rcaap.pt/detail.jsp?id=oai:www.repository.utl.pt:10400.5/6229

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universiteit Utrecht

27. 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)

Subjects/Keywords: Antibiotic resistance; hospitals; East Africa

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APA (6^th 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 (16^th Edition):

Wekesa, A N. “Prevalence of antibiotic resistance in East African Hospitals.” 2014. Masters Thesis, Universiteit Utrecht. Accessed January 18, 2020. http://dspace.library.uu.nl:8080/handle/1874/297497.

MLA Handbook (7^th Edition):

Wekesa, A N. “Prevalence of antibiotic resistance in East African Hospitals.” 2014. Web. 18 Jan 2020.

Vancouver:

Wekesa AN. Prevalence of antibiotic resistance in East African Hospitals. [Internet] [Masters thesis]. Universiteit Utrecht; 2014. [cited 2020 Jan 18]. 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

University of Sydney

28. 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)

Subjects/Keywords: Escherichia coli; Plasmid; antibiotic resistance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th 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 (16^th Edition):

Moran, Robert A. “Characterisation of plasmids in commensal Escherichia coli from healthy Australian adults .” 2018. Thesis, University of Sydney. Accessed January 18, 2020. 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 (7^th Edition):

Moran, Robert A. “Characterisation of plasmids in commensal Escherichia coli from healthy Australian adults .” 2018. Web. 18 Jan 2020.

Vancouver:

Moran RA. Characterisation of plasmids in commensal Escherichia coli from healthy Australian adults . [Internet] [Thesis]. University of Sydney; 2018. [cited 2020 Jan 18]. 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

McMaster University

29. 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 (6^th 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 (16^th Edition):

Kelso, Jayne. “Characterizing the mechanism and regulation of a rifamycin monooxygenase in Streptomyces venezuelae.” 2016. Masters Thesis, McMaster University. Accessed January 18, 2020. http://hdl.handle.net/11375/20423.

MLA Handbook (7^th Edition):

Kelso, Jayne. “Characterizing the mechanism and regulation of a rifamycin monooxygenase in Streptomyces venezuelae.” 2016. Web. 18 Jan 2020.

Vancouver:

Kelso J. Characterizing the mechanism and regulation of a rifamycin monooxygenase in Streptomyces venezuelae. [Internet] [Masters thesis]. McMaster University; 2016. [cited 2020 Jan 18]. 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

McMaster University

30. 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 (6^th 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 (16^th Edition):

Pawlowski, Andrew. “Diversity and Evolution of Antibiotic Resistomes.” 2017. Doctoral Dissertation, McMaster University. Accessed January 18, 2020. http://hdl.handle.net/11375/22808.

MLA Handbook (7^th Edition):

Pawlowski, Andrew. “Diversity and Evolution of Antibiotic Resistomes.” 2017. Web. 18 Jan 2020.

Vancouver:

Pawlowski A. Diversity and Evolution of Antibiotic Resistomes. [Internet] [Doctoral dissertation]. McMaster University; 2017. [cited 2020 Jan 18]. 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

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Open Access Theses and Dissertations