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dc.contributor.advisorCarl Nathon
dc.contributor.authorGeiger, Annie
dc.date.accessioned2019-06-28T18:08:25Z
dc.date.issued2019-05
dc.identifier.urihttps://hdl.handle.net/1813/66652
dc.description.abstractPhosphopantetheinyl transferase (PptT) is an essential enzyme in Mycobacterium tuberculosis (Mtb) that adds a pantothenate group onto carrier proteins using coenzyme A (CoA), changing them from the apo to holo enzyme configuration. Encoded for in the same operon, phosphopantetheinyl hydrolase (PptH) is a newly identified enzyme that counterbalances this reaction by removing the pantetheine group from the holo-carrier protein, resulting in an apo-carrier protein. Because PptH appears to operate a futile cycle in the cell, its purpose remains unknown. In this project, I aimed to understand the functions of PptH and the conditions in which it becomes essential in the mycobacterial cell through a series of chemical stress tests and an analysis of binding partners of PptH. Select chemical stress growth assays indicated that Mycobacterium smegmatis (Msm) strains encoding putative PptH loss-of-function (LOF) mutations possess impaired cell wall integrity. CRISPRi was used to test for synthetic lethality in the proposed role of PptH in a CoA salvage pathway. Co-IPs were not able to show that PptH and its neighboring enzyme, PptT are binding partners. These results gleam insight into mycobacterial biology, the functions of PptH, and its efficacy as a putative drug target for tuberculosis.
dc.language.isoen_US
dc.subjectBiological sciences honors program
dc.subjectMycobacteria
dc.subjecttuberculosis
dc.subjectCocnzyme A metabolism
dc.subjectphosphopantetheinyl transferase
dc.subjectphosphopantetheinyl hydrolase.
dc.subjectmycobucterial cell wall
dc.subjectCRISPRi
dc.subjectenzyme function
dc.subjectnovel mechanism of antimicrobial resistance
dc.titleAn investigation of the role of enzyme phosphopantetheinyl hydrolase in mycobacteria
dc.typedissertation or thesis
thesis.degree.disciplineBiological Sciences
thesis.degree.levelBachelor of Science
thesis.degree.nameB.S., Biological Sciences
dc.identifier.doihttps://doi.org/10.7298/1efv-s678


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