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Investigation of Bacterial Metabolic Remodeling in Response to Environmental Perturbations

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서명/저자사항Investigation of Bacterial Metabolic Remodeling in Response to Environmental Perturbations.
개인저자Pisithkul, Tippapha.
단체저자명The University of Wisconsin - Madison. Cellular & Molecular Bio - AG.
발행사항[S.l.]: The University of Wisconsin - Madison., 2018.
발행사항Ann Arbor: ProQuest Dissertations & Theses, 2018.
형태사항143 p.
기본자료 저록Dissertations Abstracts International 81-04B.
Dissertation Abstract International
ISBN9781687972873
학위논문주기Thesis (Ph.D.)--The University of Wisconsin - Madison, 2018.
일반주기 Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Amador-Noguez, Daniel.
이용제한사항This item must not be sold to any third party vendors.This item must not be added to any third party search indexes.
요약Studies of bacterial metabolism have provided insights into the pathogenic mechanism of bacterial diseases and facilitated metabolic engineering to enhance yields of valuable products. For many years, bacterial metabolism research has relied on genetics and gene expression analyses. However, it has recently been shown that transcriptional regulation alone cannot explain the observed changes in substrate-induced metabolic fluxes. Therefore, the measurement of a direct output of metabolism - metabolite concentrations and metabolic fluxes - is critical to the study of bacterial metabolism.High-performance liquid chromatography coupled with mass spectrometry emerges as key technologies that allow identification and comprehensive quantitation of metabolites. The work described in this thesis relied on the metabolomic approach to investigate bacterial metabolic responses to environmental changes. In the first part of the thesis (Chapter 2), we examined how Escherichia coli responded to the phenolic compounds found in the acid-pretreated plant biomass. We identified de novo nucleotide biosynthesis as a target of those compounds. Specifically, we demonstrated that the tested phenolics competitively inhibit glutamineamidotransferases, the enzymes that participate in the biosynthesis of nucleotides. This information could help design strategies to relieve growth inhibition of E. coli grown in the pretreated plant biomass.In contrast to the fast response/adaptation to exposure to the phenolic stressors, the second part of the thesis, described in Chapters 3 and 4, explored the temporal alterations in metabolism over the course of biofilm development in Bacillus subtilis. We combined metabolome, transcriptome, and proteome analyses to gain a holistic understanding of metabolism associated with biofilm growth. We highlighted the dynamic and significant changes in activities of several metabolic pathways and some potential regulatory components that might play roles in biofilm formation and development. We further demonstrated the importance of acetoin biosynthesis during biofilm development. Deletion of either the acetoin biosynthetic enzyme gene or its transcriptional activator led to an inability to develop complex biofilm structures. We hypothesized that acetoin biosynthesis serves as a way to produce ATP (from glycerol conversion to pyruvate, which can then be converted to acetoin) without an additional production of NADH equivalents, which is unfavorable in the anaerobic environment of pellicle biofilms.
일반주제명Microbiology.
Analytical chemistry.
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