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mntP 和 yiiP 有助于鼠伤寒沙门氏菌血清型在锰过载和硝化应激条件下的锰外排。

MntP and YiiP Contribute to Manganese Efflux in Salmonella enterica Serovar Typhimurium under Conditions of Manganese Overload and Nitrosative Stress.

机构信息

Rhodes Collegegrid.262541.6 Biology Department, Memphis, Tennessee, USA.

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbournegrid.1008.9, Victoria, Australia.

出版信息

Microbiol Spectr. 2022 Feb 23;10(1):e0131621. doi: 10.1128/spectrum.01316-21. Epub 2022 Jan 12.

Abstract

The divalent transition metal cation manganese is important for protein function, particularly under conditions of iron limitation, nitrosative stress, and oxidative stress, but can mediate substantial toxicity in excess. Salmonella enterica serovar Typhimurium possesses multiple manganese importers, but the pathways for manganese efflux remain poorly defined. The . Typhimurium ATCC 14028s genome was analyzed for putative manganese export pathways, which identified a previously uncharacterized homologue of the Escherichia coli manganese exporter , and two cation diffusion facilitator family transporters, () and (). Manganese acquisition by . Typhimurium has been shown to occur in response to nitric oxide, an important chemical mediator of the mammalian innate immune response. However, cellular manganese can rapidly return to prechallenge levels, strongly suggesting that one or more . Typhimurium exporters may contribute to this process. Here, we report that and contribute to manganese resistance and export in . Typhimurium. YiiP, also known as FieF, has previously been associated with zinc and iron transport, although its physiological role remains ambiguous due to a lack of zinc-sensitive phenotypes in mutant strains of . Typhimurium and E. coli. We report that . Typhimurium Δ Δ mutants are exquisitely sensitive to manganese and show that both YiiP and MntP contribute to manganese efflux following nitric oxide exposure. Transition metal cations are required for the function of many proteins but can mediate toxicity when present in excess. Identifying transporters that facilitate metal ion export, the conditions under which they are expressed, and the role they play in bacterial physiology is an evolving area of interest for environmental and pathogenic organisms. Determining the native targets of metal transporters has proved challenging since bioinformatic predictions, transport data, and mutant phenotypes do not always agree. This work identifies two transporters that mediate manganese efflux from the Gram-negative pathogen Salmonella enterica serovar Typhimurium in response to manganese overload and nitric oxide stress. While homologues of MntP have been characterized previously, this is the first observation of YiiP contributing to manganese export.

摘要

二价过渡金属阳离子锰对于蛋白质功能很重要,特别是在铁限制、硝化应激和氧化应激条件下,但过量会导致严重毒性。鼠伤寒沙门氏菌具有多种锰转运体,但锰外排途径仍不清楚。分析了. Typhimurium ATCC 14028s 基因组中可能的锰外排途径,鉴定出大肠杆菌锰外排蛋白的一个以前未描述的同源物,以及两个阳离子扩散促进剂家族转运蛋白 () 和 ()。已经表明,鼠伤寒沙门氏菌通过一氧化氮(哺乳动物先天免疫反应的重要化学介质)获得锰。然而,细胞内锰可以迅速恢复到挑战前的水平,这强烈表明一个或多个. Typhimurium 外排泵可能有助于这一过程。在这里,我们报告 YiiP 和 MntP 有助于鼠伤寒沙门氏菌的锰抗性和外排。YiiP,也称为 FieF,先前与锌和铁的运输有关,尽管由于鼠伤寒沙门氏菌和大肠杆菌突变株缺乏锌敏感表型,其生理作用仍不清楚。我们报告. Typhimurium Δ Δ 突变体对锰极其敏感,并表明一氧化氮暴露后 YiiP 和 MntP 都有助于锰外排。过渡金属阳离子是许多蛋白质功能所必需的,但当过量存在时会介导毒性。确定促进金属离子外排的转运蛋白、它们表达的条件以及它们在细菌生理学中的作用,是环境和致病生物的一个不断发展的研究领域。确定金属转运蛋白的天然靶标一直具有挑战性,因为生物信息学预测、转运数据和突变表型并不总是一致。这项工作鉴定了两种转运蛋白,它们可以响应锰过载和一氧化氮应激,从革兰氏阴性病原体鼠伤寒沙门氏菌中排出锰。虽然 MntP 的同源物以前已经被描述过,但这是首次观察到 YiiP 有助于锰的外排。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82c6/8754126/6de7b8e6fa4a/spectrum.01316-21-f001.jpg

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