자료유형 | 학위논문 |
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서명/저자사항 | The Response of Acinetobacter baumannii to Calprotectin Induced Multi-Metal Restriction. |
개인저자 | Wang, Jiefei. |
단체저자명 | Indiana University. Biochemistry. |
발행사항 | [S.l.]: Indiana University., 2019. |
발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
형태사항 | 244 p. |
기본자료 저록 | Dissertations Abstracts International 81-03B. Dissertation Abstract International |
ISBN | 9781088381120 |
학위논문주기 | Thesis (Ph.D.)--Indiana University, 2019. |
일반주기 |
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Giedroc, David P. |
이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
요약 | Transition metals execute key catalytic, structural, and regulatory functions that broadly impact all phases of microbial cellular physiology. The mammalian host takes advantage of this essentiality by restricting growth of invading pathogens through a process termed nutritional immunity, in which transition metals are withheld from microbial invaders by mammalian metal binding proteins. Host neutrophils secrete calprotectin (CP), which is a versatile metal-sequestering protein that forms high thermodynamic and/or kinetic stability coordination complexes with d-block metals. The physiological impact of CP is expected to be niche- and pathogen-dependent, but little is known about how CP induced stress impacts metabolism in different pathogens. Acinetobacter baumannii is a Gram-negative bacterial pathogen commonly associated with hospital-acquired infections. CP treatment of A. baumannii strongly restricts the availability of zinc and iron. The bacteria respond by inducing an acute cellular response to zinc and iron deficiency while limiting the bioavailability of copper. We investigated periplasmic and cytoplasmic metabolism of A. baumannii under CP-induced multi-metal starvation. First, we characterized a Zur regulated lipoprotein, ZrlA, and elucidated a new link between cell wall homeostasis and Zn uptake in A. baumannii through the action of ZrlA. Second, we found histidine utilization genes are upregulated to degrade His in order to liberate Zn to from a labile Zn-His pool, and we characterized GTPase ZigA, which may function as a metallochaperone required for HutH degradation of His. Third, using zigA deletion strain as a tool to investigate how A. baumannii responds to extreme metal starvation induced by CP, we observed an incrementally increased abundance of RibBX and RibB as proxy for cellular efforts to ensure sufficient flavin supply. The comprehensive study on how A. baumannii response to CP-induced metal starvation expands insight of relationship between and highlights the therapeutic potential of targeting metal homeostasis systems and bacterial cellular metabolism pathways. |
일반주제명 | Biochemistry. |
언어 | 영어 |
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