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Rutgers University
1.
Al-Tameemi, Hassan Mohammed Jasim, 1977-.
Transition metals homeostasis in Staphylococcus aureus.
Degree: PhD, Microbial Biology, 2019, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/61680/ 
► Staphylococcus aureus is a public health concern. It can evade the immune system and develop resistance to many antibiotic classes. The human immune system employs…
(more)
▼ Staphylococcus aureus is a public health concern. It can evade the immune system and develop resistance to many antibiotic classes. The human immune system employs diverse mechanisms to overcome S. aureus infections including disrupting iron (Fe) and copper (Cu) homeostasis at the host-pathogen interface. The work presented herein described iron-sulfur (Fe-S) cluster synthesis as a potential antimicrobial target. We demonstrated that Suf (sulfur mobilization)-dependent Fe-S cluster synthesis is essential in S. aureus. Importantly, the Suf system is not present in mammals suggesting that it is a promising antibiotic target. A strain with decreased suf transcription exhibited phenotypes that are associated with impaired Fe-S protein maturation. These phenotypes included a reduction in the activity of Fe-S cluster-dependent enzymes and growth inhibition in media deficient in metabolites that require Fe-S enzymes for synthesis. The impairment in Fe-S cluster biogenesis led to increased sensitivity to reactive oxygen and reactive nitrogen species and decreased survival in human polymorphonuclear leukocytes. We explored how copper harm S. aureus, by creating a ΔcopAB ΔcopBL strain (cop-) that was defective in removing copper from the cytosol. We isolated cop- strains with Tn insertions in mntABC that resist copper. When cultured with copper, strains containing the mntA::Tn mutation had less copper load than the parent strains. Manganese bound MntR repressed MntABC. The ?mntR strain had reduced growth and increased copper load under copper stress. The introduction of the mntA::Tn allele annulled these phenotypes. Over-expression of MntABC amplified cellular copper load and sensitivity to copper. The mntA::Tn mutation presence also protected Fe-S enzymes from inactivation by copper. We also found that copper was not substantially inhibiting the growth of S. aureus by poisoning NrdEF under the growth conditions utilized; however, when NrdEF function was decreased by copper, the ribonucleotide reductase function is decreased by the addition of hydroxyurea. The introduction of a mntA::Tn allele improved growth of both ΔcopAZ and ΔcopBL strains from copper intoxication suggesting that the presence of a second copper detoxification system protects S. aureus from MntABC-dependent copper intoxication. The data presented are consistent with a model wherein copper enters S. aureus cells via the MntABC importer and poisons Fe-S enzymes. Taken together, the work presented in this thesis supports the viability of targeting Fe-S synthesis as a viable therapeutic approach and established a novel role for mntABC in copper homeostasis.
Advisors/Committee Members: Boyd, Jeffrey M (chair), Zylstra, Gerben J (internal member), Barkay, Tamar (internal member), Toledo, Alvaro (outside member), School of Graduate Studies.
Subjects/Keywords: Metals homeostasis; Staphylococcus aureus
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APA (6th Edition):
Al-Tameemi, Hassan Mohammed Jasim, 1. (2019). Transition metals homeostasis in Staphylococcus aureus. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/61680/
Chicago Manual of Style (16th Edition):
Al-Tameemi, Hassan Mohammed Jasim, 1977-. “Transition metals homeostasis in Staphylococcus aureus.” 2019. Doctoral Dissertation, Rutgers University. Accessed January 16, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/61680/.
MLA Handbook (7th Edition):
Al-Tameemi, Hassan Mohammed Jasim, 1977-. “Transition metals homeostasis in Staphylococcus aureus.” 2019. Web. 16 Jan 2021.
Vancouver:
Al-Tameemi, Hassan Mohammed Jasim 1. Transition metals homeostasis in Staphylococcus aureus. [Internet] [Doctoral dissertation]. Rutgers University; 2019. [cited 2021 Jan 16].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/61680/.
Council of Science Editors:
Al-Tameemi, Hassan Mohammed Jasim 1. Transition metals homeostasis in Staphylococcus aureus. [Doctoral Dissertation]. Rutgers University; 2019. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/61680/
Rutgers University
2.
Bhatt, Shiven K., 1986-.
Gaining insight into the maturation of iron-sulfur (FeS) clusters in staphylococcus aureus by determining the role of DUF59 protein, SufT.
Degree: MS, Microbial Biology, 2018, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/55980/
► Staphylococcus aureus is a serious mammalian pathogen. For Staphylococcus aureus to successfully inflict pathogenesis upon a host, it is imperative for it to acquire and…
(more)
▼ Staphylococcus aureus is a serious mammalian pathogen. For Staphylococcus aureus to successfully inflict pathogenesis upon a host, it is imperative for it to acquire and effectively utilize iron (Fe). Once Fe is internalized, S. aureus utilizes the SUF system to assemble small inorganic cofactors called iron-sulfur (FeS) clusters. FeS clusters have a wide variety of functions in cells, thus, defective FeS cluster assembly results in global metabolic defects. In addition, FeS cluster synthesis and the assembly of FeS proteins is essential in S. aureus and a number of alternate bacterial pathogens suggesting that it is a viable antimicrobial target. Proteins containing DUF59 domains have roles in FeS cluster assembly and are found throughout Eukarya, Bacteria and Archaea. However, the function of DUF59 remains unknown in S. aureus. We have identified the S. aureus SufT, which is composed solely of the DUF59 domain and demonstrated that it has a role in the maturation of iron-sulfur (FeS) proteins.
Advisors/Committee Members: Boyd, Jeffrey M (chair), Barkay, Tamar (internal member), Zylstra, Gerben (internal member), School of Graduate Studies.
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APA (6th Edition):
Bhatt, Shiven K., 1. (2018). Gaining insight into the maturation of iron-sulfur (FeS) clusters in staphylococcus aureus by determining the role of DUF59 protein, SufT. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/55980/
Chicago Manual of Style (16th Edition):
Bhatt, Shiven K., 1986-. “Gaining insight into the maturation of iron-sulfur (FeS) clusters in staphylococcus aureus by determining the role of DUF59 protein, SufT.” 2018. Masters Thesis, Rutgers University. Accessed January 16, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/55980/.
MLA Handbook (7th Edition):
Bhatt, Shiven K., 1986-. “Gaining insight into the maturation of iron-sulfur (FeS) clusters in staphylococcus aureus by determining the role of DUF59 protein, SufT.” 2018. Web. 16 Jan 2021.
Vancouver:
Bhatt, Shiven K. 1. Gaining insight into the maturation of iron-sulfur (FeS) clusters in staphylococcus aureus by determining the role of DUF59 protein, SufT. [Internet] [Masters thesis]. Rutgers University; 2018. [cited 2021 Jan 16].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/55980/.
Council of Science Editors:
Bhatt, Shiven K. 1. Gaining insight into the maturation of iron-sulfur (FeS) clusters in staphylococcus aureus by determining the role of DUF59 protein, SufT. [Masters Thesis]. Rutgers University; 2018. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/55980/
Rutgers University
3.
Zhang, Yuan, 1990-.
From light to life: the energy conversion and storage in plants and algae.
Degree: PhD, Microbial Biology, 2018, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/59289/
► Photosynthesis, the physico-chemical process converting sunlight into chemical energy, is the basis to feed the world and fuel the planet. To satisfy the growing demand…
(more)
▼ Photosynthesis, the physico-chemical process converting sunlight into chemical energy, is the basis to feed the world and fuel the planet. To satisfy the growing demand for food and fuel, the efficiency of the natural photosynthesis needs to be optimized for maximum crop yield, while the photosynthetically assimilated carbon needs to be more sophisticatedly recruited for generating energy-dense renewable products. There are two objectives of this dissertation, the first is to explore the feasibility to boost biomass yield of crop plants by genetically engineering their photosystem II (PSII), and the second is to create robust microalgal transgenic strains with enhanced lipid content and CO2 utilization efficiency, which will contribute to microalgal biofuel production as well as CO2 mitigation.
In Chapter 2, we explore whether the prokaryotic design principal of PSII D1 subunit is applicable in a higher plant model Nicotiana tabacum. By introducing single point mutations into tobacco psbA gene (coding for the reaction center D1 subunit of Photosystem II) to mimic the cyanobacterial high-light and low-light D1 isoforms, the tobacco mutants exhibit the biophysical traits of the prokaryotic PSII. The tobacco mutant expressing the engineered high light isoform exhibits higher photosynthetic efficiency, higher tolerance to photoinhibition and increased biomass production under the tested light conditions. The only benefit of incorporating the cyanobacterial low light mutation into tobacco D1 protein is restricted to improving the Water Oxidizing Complex catalytic efficiency at low light intensity, while the biomass yield was impaired at all the tested light conditions.
In Chapter 3, Nannochloropsis oceanica CCMP1779 (N.o1779), the emerging oleaginous model alga, is chosen for application of the “push and pull” strategy to enhance its lipid productivity by metabolic engineering. The regulatory importance of citrate synthase (CIS) in directing carbon flux towards protein synthesis pathway, and the functional role of glycerol 3-phosphate dehydrogenase (G3PDH) in diverting carbon precursors from glycolysis to TAG assembly are fully examined in the transgenic strains of N.o1779. Downregulation of a putative endogenous gene encoding CIS via RNA interference technology and expression of a yeast gene encoding the cytosolic G3PDH lead to higher accumulation of the storage lipid triacylglycerols (TAGs) and increased abundance of the lipid building block free fatty acids, advancing our understanding of the genetic and molecular basis of algal TAG metabolism.
In Chapter 4, the goal was to create a robust industrial strain that can be cultivated in the open culture using flue gas as carbon source. By applying insertional mutagenesis combined with high-throughput screening strategy to the oleaginous microalga N.o1779, a winning mutant was successfully identified for its advantages in photoautotrophic growth and intrinsic photosynthetic efficiency under both normal growth condition and acidic environment. The genome sequencing project…
Advisors/Committee Members: Dismukes, G. Charles (chair), Bhattacharya, Debashish (internal member), Boyd, Jeffrey M. (internal member), Maliga, Pal (outside member), School of Graduate Studies.
Subjects/Keywords: Biomass energy; Microalgae
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APA (6th Edition):
Zhang, Yuan, 1. (2018). From light to life: the energy conversion and storage in plants and algae. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/59289/
Chicago Manual of Style (16th Edition):
Zhang, Yuan, 1990-. “From light to life: the energy conversion and storage in plants and algae.” 2018. Doctoral Dissertation, Rutgers University. Accessed January 16, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/59289/.
MLA Handbook (7th Edition):
Zhang, Yuan, 1990-. “From light to life: the energy conversion and storage in plants and algae.” 2018. Web. 16 Jan 2021.
Vancouver:
Zhang, Yuan 1. From light to life: the energy conversion and storage in plants and algae. [Internet] [Doctoral dissertation]. Rutgers University; 2018. [cited 2021 Jan 16].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/59289/.
Council of Science Editors:
Zhang, Yuan 1. From light to life: the energy conversion and storage in plants and algae. [Doctoral Dissertation]. Rutgers University; 2018. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/59289/
4.
Mashruwala, Ameya Ashutosh, 1983-.
The influence of oxygen upon the lifestyle choices of Staphylococcus aureus.
Degree: PhD, Microbial Biology, 2017, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/53737/
► Biofilms are communities of microorganisms attached to a surface or each other. Biofilm associated cells are the etiologic agents of recurrent Staphylococcus aureus infections. Oxygen…
(more)
▼ Biofilms are communities of microorganisms attached to a surface or each other. Biofilm associated cells are the etiologic agents of recurrent Staphylococcus aureus infections. Oxygen is utilized by S. aureus as a terminal electron acceptor (TEA). Infected human tissues are hypoxic or anoxic. S. aureus increases biofilm formation in response to hypoxia, but how this occurs is unknown. This thesis reports that oxygen influences biofilm formation in its capacity as a TEA for cellular respiration. Genetic, physiological, or chemical inhibition of respiratory processes elicited increased biofilm formation. Impaired respiration led to increased cell lysis via divergent regulation of two processes: increased expression of the AtlA murein hydrolase and decreased expression of the AtlA-inhibitory glycopolymers, WTA. The AltA-dependent release of cytosolic DNA contributed to increased biofilm formation. The fibronectin binding protein A, which is known to interact with AtlA, was also found to be involved in fermentative biofilm formation. Further, cell lysis and biofilm formation were governed by the SrrAB and the SaeRS two-component regulatory systems (TCRS). Genetic evidence suggests that SrrAB-dependent biofilm formation occurs in response to the accumulation of reduced menaquinone. SaeRS-dependent biofilm formation also occurred in response to changes in the respiratory status of the cell, via an as yet undefined signal molecule(s). Further, a high cellular titer of phosphorylated SaeR is required for biofilm formation. Epistasis analyses found that SaeRS and SrrAB influence biofilm formation independent of one another, in vitro. SrrAB and SaeRS governed host colonization in vivo, in the context of a mouse model of orthopedic implant-associated biofilm formation. Of these two TCRS, SrrAB is the dominant system driving biofilm formation in vivo. Biofilms impart protection from innate immunity as well as therapeutic agents. Data presented suggest that pre-formed biofilms, established by fermenting S. aureus, can be prompted to detach and disperse upon exposure to a TEA (oxygen or nitrate). Exposure to oxygen (reaeration) results in increased growth but decreased transcription of atlA and decreased release of DNA. Reaeration is also accompanied by increased transcription of sspA which encodes for a protease capable of cleaving AtlA. Biofilm dispersal was blocked in a strain that is incapable of respiration, suggesting changes in cellular respiratory status are being sensed to trigger dispersal. The transcription of atlA and sspA upon reaeration was modulated in a divergent manner by SrrAB. Data presented suggest that SrrAB achieves divergent regulation of atlA, in two separate growth conditions, via the small RNA, rsaE, as an intermediary. In summation, the results presented define the bases for how oxygen dictates the lifestyle choices of S. aureus. The studies also establish the mechanistic and regulatory bases underlying the formation of anaerobic and fermentative biofilms by S. aureus.
Advisors/Committee Members: Boyd, Jeffrey M (chair), Belden, William J (internal member), Bhattacharya, Debashish (internal member), Stock, Ann M (outside member).
Subjects/Keywords: Staphylococcus aureus infections; Biofilms
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APA (6th Edition):
Mashruwala, Ameya Ashutosh, 1. (2017). The influence of oxygen upon the lifestyle choices of Staphylococcus aureus. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/53737/
Chicago Manual of Style (16th Edition):
Mashruwala, Ameya Ashutosh, 1983-. “The influence of oxygen upon the lifestyle choices of Staphylococcus aureus.” 2017. Doctoral Dissertation, Rutgers University. Accessed January 16, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/53737/.
MLA Handbook (7th Edition):
Mashruwala, Ameya Ashutosh, 1983-. “The influence of oxygen upon the lifestyle choices of Staphylococcus aureus.” 2017. Web. 16 Jan 2021.
Vancouver:
Mashruwala, Ameya Ashutosh 1. The influence of oxygen upon the lifestyle choices of Staphylococcus aureus. [Internet] [Doctoral dissertation]. Rutgers University; 2017. [cited 2021 Jan 16].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/53737/.
Council of Science Editors:
Mashruwala, Ameya Ashutosh 1. The influence of oxygen upon the lifestyle choices of Staphylococcus aureus. [Doctoral Dissertation]. Rutgers University; 2017. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/53737/
5.
Greendyk, Julia Renee, 1993-.
Genome scale tracking of Mycobacterium tuberculosis MazF toxin targets.
Degree: MS, Microbial Biology, 2017, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/55482/
► Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB), claims millions of lives every year. Due to coinfection of TB and HIV, increasing antibiotic resistance, and…
(more)
▼ Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB), claims millions of lives every year. Due to coinfection of TB and HIV, increasing antibiotic resistance, and the unique ability of
M. tuberculosis to persist in a non-replicating state within its host as a latent infection, TB eradication attempts have consistently failed. Latent TB infects one-third of the world’s population and is refractory to many antibiotics, yet the molecular mechanisms by which
M. tuberculosis enters and maintains latency are poorly understood. However, members of the MazF family of toxins, which act by cleaving specific regions of single-stranded RNA, are implicated in this process. To help elucidate the role that MazF toxins play in latent tuberculosis, we used a novel RNA-sequencing approach, 5’RNA-seq, to determine the RNA targets of 4
M. tuberculosis MazF toxins. While MazF-mt10 cleaved at a specific consensus sequence, CACCU, MazF-mt4, -mt7, and -mt11 did not appear to cleave at a specific sequence. MazF-mt7 cleaved at a number of positions within 23S rRNA; degradation of 23S rRNA could serve as a potent mechanism by which to inhibit translation and modulate growth. MazF-mt7 and -mt10 cleaved 16S rRNA slightly upstream of the 3’ end, thus removing the anti-Shine-Dalgarno sequence and potentially aiding in the formation of stress ribosomes that can preferentially translate leaderless mRNAs in
M. tuberculosis. MazF-mt4, -mt7 and –mt11 cleaved distinct tRNAs at their anticodon stem loop, providing another way through which to regulate translation. Results from this study could lead to the identification of MazF-related biomarkers for latent tuberculosis, which could in turn be used to develop new, more effective antimicrobials to fight latent tuberculosis.
Advisors/Committee Members: Woychik, Nancy A (chair), Bhattacharya, Debashish (internal member), Boyd, Jeffrey M (internal member), Zylstra, Gerben J (internal member), School of Graduate Studies.
Subjects/Keywords: Mycobacterium tuberculosis
…Schatz
discovered the soil microorganism Streptomyces griseus at Rutgers University;
this led…
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APA (6th Edition):
Greendyk, Julia Renee, 1. (2017). Genome scale tracking of Mycobacterium tuberculosis MazF toxin targets. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/55482/
Chicago Manual of Style (16th Edition):
Greendyk, Julia Renee, 1993-. “Genome scale tracking of Mycobacterium tuberculosis MazF toxin targets.” 2017. Masters Thesis, Rutgers University. Accessed January 16, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/55482/.
MLA Handbook (7th Edition):
Greendyk, Julia Renee, 1993-. “Genome scale tracking of Mycobacterium tuberculosis MazF toxin targets.” 2017. Web. 16 Jan 2021.
Vancouver:
Greendyk, Julia Renee 1. Genome scale tracking of Mycobacterium tuberculosis MazF toxin targets. [Internet] [Masters thesis]. Rutgers University; 2017. [cited 2021 Jan 16].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/55482/.
Council of Science Editors:
Greendyk, Julia Renee 1. Genome scale tracking of Mycobacterium tuberculosis MazF toxin targets. [Masters Thesis]. Rutgers University; 2017. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/55482/
Rutgers University
6.
Rosario-Cruz, Zuelay E., 1987-.
Insights into mechanisms of metal homeostasis in Staphylococcus aureus.
Degree: PhD, Microbial Biology, 2016, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/50143/
► Staphylococcus aureus is a major public health concern worldwide. The human immune system employs oxidative- and copper-dependent mechanisms that disrupt metal homeostasis within the invading…
(more)
▼ Staphylococcus aureus is a major public health concern worldwide. The human immune system employs oxidative- and copper-dependent mechanisms that disrupt metal homeostasis within the invading microorganism. This thesis describes new factors involved in iron-sulfur cluster biogenesis and copper detoxification in S. aureus, representing additional mechanisms of metal homeostasis that might aid this pathogen during host infection. Strains lacking the low-molecular-weight thiol bacillithiol (bshA mutants) display growth defects that are alleviated by the addition of exogenous Fe or the amino acids leucine and isoleucine. The bshA strain has decreased activities of Fe-S proteins, such as LeuCD, IlvD, AcnA, and GltBD, suggesting that the absence of BSH leads to a general defect in Fe-S cluster biogenesis. The growth defects and decreased enzymatic activities of the bshA strain are exacerbated in strains lacking other factors involved in Fe-S cluster biogenesis, such as the Fe-S cluster carriers Nfu and SufA, and partially suppressed by their overexpression, suggesting a functional overlap between BSH and Fe-S cluster carriers in Fe-S cluster biogenesis. We also found a two-gene operon involved in preventing copper (Cu) intoxication. These genes encode an ATPase Cu transporter (copB) and a putative lipoprotein (cbl). Mutational inactivation of copB or cbl resulted in Cu sensitivity, and their phenotypes are exacerbated in strains also lacking the highly conserved Cu exporter CopA, suggesting that CopB and Cbl are additional mechanisms that prevent Cu intoxication in S. aureus. Overexpression of either copB or cbl leads to increased Cu resistance in other S. aureus clinical isolates lacking these genes. We show that copB and cbl are co-transcribed, up-regulated under Cu stress, and repressed by CsoR. Genetic and biochemical evidence show that Cbl is a membrane-associated, surface-exposed lipoprotein that binds up to four Cu+ ions. Collectively, the research presented in this thesis describes new roles for BSH and Cbl in metal homeostasis in the human pathogen S. aureus.
Advisors/Committee Members: Boyd, Jeffrey M (chair), Leustek, Thomas (internal member), Kobayashi, Donald Y (internal member), Belden, William B (outside member).
Subjects/Keywords: Staphylococcus aureus; Homeostasis
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APA (6th Edition):
Rosario-Cruz, Zuelay E., 1. (2016). Insights into mechanisms of metal homeostasis in Staphylococcus aureus. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/50143/
Chicago Manual of Style (16th Edition):
Rosario-Cruz, Zuelay E., 1987-. “Insights into mechanisms of metal homeostasis in Staphylococcus aureus.” 2016. Doctoral Dissertation, Rutgers University. Accessed January 16, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/50143/.
MLA Handbook (7th Edition):
Rosario-Cruz, Zuelay E., 1987-. “Insights into mechanisms of metal homeostasis in Staphylococcus aureus.” 2016. Web. 16 Jan 2021.
Vancouver:
Rosario-Cruz, Zuelay E. 1. Insights into mechanisms of metal homeostasis in Staphylococcus aureus. [Internet] [Doctoral dissertation]. Rutgers University; 2016. [cited 2021 Jan 16].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/50143/.
Council of Science Editors:
Rosario-Cruz, Zuelay E. 1. Insights into mechanisms of metal homeostasis in Staphylococcus aureus. [Doctoral Dissertation]. Rutgers University; 2016. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/50143/
Rutgers University
7.
Roberts, Christina.
The suf iron-sulfur cluster biosynthetic system is essential for staphylococcus aureus viability and decreased suf function results in global metbolic defects and decreased survival in human neutrophils.
Degree: MS, Microbiology and Molecular Genetics, 2016, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/51450/
► Staphylococcus aureus remains a causative agent for morbidity and mortality worldwide. This is in part a result of antimicrobial resistance highlighting the need to uncover…
(more)
▼ Staphylococcus aureus remains a causative agent for morbidity and mortality worldwide. This is in part a result of antimicrobial resistance highlighting the need to uncover novel antibiotic targets and discover new therapeutic agents. In this study we explored the possibility of iron-sulfur (FeS) cluster synthesis as a viable antimicrobial target. RNA interference studies verified that Suf-dependent FeS cluster synthesis was essential in S. aureus. Two S. aureus strains were characterized that contained transposon insertions between suf genes (suf*) resulting in decreased transcription of genes downstream of the insertions. We found that the sufCDSUB genes were cotranscribed and suf transcription was positively influenced by general stress sigma factor B. The suf* strains had decreased activities of FeS cluster-requiring enzymes and decreased growth in media lacking metabolites that require FeS proteins for synthesis. Decreased FeS cluster synthesis also resulted in sensitivity to reactive oxygen and reactive nitrogen species. Decreased Suf function resulted in increased DNA damage and defective DNA repair. It also resulted in decreased flux though the TCA cycle and decreased cellular respiration. The suf* mutants had perturbed intracellular non-chelated Fe pools. Defective FeS cluster synthesis did not alter exoprotein production or biofilm formation, but it did result in decreased survival upon challenge with human polymorphonuclear leukocytes. The results presented suggest that FeS cluster synthesis is a viable target for antimicrobial development. The strains and DNA constructs described provide a genetic toolbox for further examination of FeS cluster synthesis in S. aureus.
Advisors/Committee Members: Boyd, Jeffrey M (chair), Zylstra, Gerben (internal member), Kerkhof, Lee (internal member).
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APA (6th Edition):
Roberts, C. (2016). The suf iron-sulfur cluster biosynthetic system is essential for staphylococcus aureus viability and decreased suf function results in global metbolic defects and decreased survival in human neutrophils. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/51450/
Chicago Manual of Style (16th Edition):
Roberts, Christina. “The suf iron-sulfur cluster biosynthetic system is essential for staphylococcus aureus viability and decreased suf function results in global metbolic defects and decreased survival in human neutrophils.” 2016. Masters Thesis, Rutgers University. Accessed January 16, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/51450/.
MLA Handbook (7th Edition):
Roberts, Christina. “The suf iron-sulfur cluster biosynthetic system is essential for staphylococcus aureus viability and decreased suf function results in global metbolic defects and decreased survival in human neutrophils.” 2016. Web. 16 Jan 2021.
Vancouver:
Roberts C. The suf iron-sulfur cluster biosynthetic system is essential for staphylococcus aureus viability and decreased suf function results in global metbolic defects and decreased survival in human neutrophils. [Internet] [Masters thesis]. Rutgers University; 2016. [cited 2021 Jan 16].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/51450/.
Council of Science Editors:
Roberts C. The suf iron-sulfur cluster biosynthetic system is essential for staphylococcus aureus viability and decreased suf function results in global metbolic defects and decreased survival in human neutrophils. [Masters Thesis]. Rutgers University; 2016. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/51450/
. 
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