The Universal Stress Proteins of Micrococcus Luteus Are Metabolic Regulators That Confer Resistance to a Diverse Set of Stress Factors

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dc.contributor.advisorWidger, William R.
dc.contributor.committeeMemberŞen, Mehmet
dc.contributor.committeeMemberBawa-Khalfe, Tasneem
dc.contributor.committeeMemberMay, Elebeoba E.
dc.creatorRangel, Jonathan
dc.date.accessioned2022-06-17T21:57:22Z
dc.date.createdDecember 2021
dc.date.issued2021-12
dc.date.submittedDecember 2021
dc.date.updated2022-06-17T21:57:23Z
dc.description.abstractThe bacterial stress response systems have developed and evolved over the millennia to deal with the changing environmental conditions experienced by all the bacterial species. A common form of stress mitigation is the development of the dormant phenotype, a process by which bacteria enter a state of sustained arrested growth that renders them nearly impervious to most stress conditions including antibiotics. The dormancy state presents a growing problem in the medical field as it is implied to be one of the root causes behind chronic infections including latent Mycobacterium tuberculosis. The biochemical mechanisms that regulate the differentiation into dormancy are not fully understood, but a common link points to the possible role of universal stress proteins as a major contributor to the maintenance of the dormant phenotype. The universal stress proteins are a class of proteins that have been identified as being highly upregulated during stress response in a variety of bacteria and have been shown to be vital in maintaining cell viability during stress conditions. Our previous work has established that Micrococcus luteus presents a model example of the dormancy phenotype and that the universal stress protein (WP_010079616.1) is vital to maintain cell viability during the hypoxic induced dormant state. We have previously identified that the universal stress protein (WP_010079712.1) helps regulate growth during the initial inoculation stages alongside a resuscitation-promoting factor protein. A genetic knockout of universal stress protein (WP_010080184.1) increased the susceptibility to hydrogen peroxide stress and cause the cells to increase biofilm production during nutrient starvation. RNASeq analysis of the nutrient starved ML_Δusp616::kan transcriptome revealed a dysregulation of multiple resistance mechanisms by failing to suppress transposable elements, failing to downregulate metabolic processes, and loss of Rho transcription factor control through failure to upregulate NusG. Characterization of the Usp616 revealed that is both a homodimer forming and ATP binding variant of Usp. M. luteus is a model organism for determining the mechanisms by which Usps regulate stress response including the entering the VBNC state.
dc.description.departmentBiology and Biochemistry, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.citationPortions of this document appear in: Mali, S., Mitchell, M., Havis, S., Bodunrin, A., Rangel, J., Olson, G., Widger, W. R., and Bark, S. J. (2017) A proteomic signature of dormancy in the Actinobacterium Micrococcus luteus. J. Bacteriol. 199, e00206-00217; and in: Havis, S., Bodunrin, A., Rangel, J., Zimmerer, R., Murphy, J., Storey, J. D., Duong, T. D., Mistretta, B., Gunaratne, P., Widger, W. R., and Bark, S. J. (2019) A universal stress protein that controls bacterial stress survival in Micrococcus luteus. J. Bacteriol. 201, e00497-00419; and in: Bodunrin, A. (2020) Micrococcus luteus UspA-like protein Usp712 controls exponential growth by up regulation of required pathways including resuscitation promoting factor. ProQuest Dissertations Publishing. PhD Dissertation. University of Houston; and in: Havis, S., Rangel, J., Mali, S., Bodunrin, A., Housammy, Z., Zimmerer, R., Murphy, J., Widger, W. R., and Bark, S. J. (2019) A color-based competition assay for studying bacterial stress responses in Micrococcus luteus. FEMS Microbiol. Lett. 366, fnz054
dc.identifier.urihttps://hdl.handle.net/10657/9269
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectbacterial stress response, dormancy, VBNC, universal stress proteins, Tuberculosis,
dc.titleThe Universal Stress Proteins of Micrococcus Luteus Are Metabolic Regulators That Confer Resistance to a Diverse Set of Stress Factors
dc.type.dcmiText
dc.type.genreThesis
dcterms.accessRightsThe full text of this item is not available at this time because the student has placed this item under an embargo for a period of time. The Libraries are not authorized to provide a copy of this work during the embargo period.
local.embargo.lift2023-12-01
local.embargo.terms2023-12-01
thesis.degree.collegeCollege of Natural Sciences and Mathematics
thesis.degree.departmentBiology and Biochemistry, Department of
thesis.degree.disciplineBiochemistry
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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