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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
Descriptive
TitleInfo
Title
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
Name
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Roberts
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Christina
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Christina Roberts
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author
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Boyd
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Jeffrey M
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Jeffrey M Boyd
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Advisory Committee
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chair
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Zylstra
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Gerben
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Gerben Zylstra
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Advisory Committee
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internal member
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Kerkhof
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Lee
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Lee Kerkhof
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Advisory Committee
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internal member
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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theses
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2016
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2016-10
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2016
Place
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xx
Language
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eng
Abstract
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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.
Subject
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Topic
Microbiology and Molecular Genetics
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Rutgers University Electronic Theses and Dissertations
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ETD_7599
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electronic resource
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application/pdf
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1 online resource (xxiv, 33 p. : ill.)
Note
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M.S.
Note
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Includes bibliographical references
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by Chistina Roberts
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
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doi:10.7282/T3W37ZMH
Genre
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ETD graduate
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
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Roberts
GivenName
Christina
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Permission or license
DateTime
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2016-09-20 19:07:07
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Name
Christina Roberts
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Rutgers University. Graduate School - New Brunswick
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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2016-10-31
DateTime
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2017-10-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2017.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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