Phosphorylation-dependent and Phosphorylation-independent Regulation of Helicobacter pylori Acid Acclimation by the ArsRS Two-component System.
Phosphorylation-dependent and Phosphorylation-independent Regulation of Helicobacter pylori Acid Acclimation by the ArsRS Two-component System.
复制标题
ArsRS 双组分系统对幽门螺杆菌酸驯化的磷酸化依赖性和磷酸化非依赖性调节。
DOI：
10.1111/hel.12235
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发表时间：
2016
期刊：
影响因子：
4.4
通讯作者：
Scott,DavidR
中科院分区：
文献类型：
--
作者：
Marcus,ElizabethA;Sachs,George;Wen,Yi;Scott,DavidR
背景pH敏感的幽门螺杆菌ArsRS双组分系统（TCS）通过直接感知和响应环境酸度来帮助这种嗜中性粒细胞在胃环境中存活。ArsS是酸诱导的尿素酶及其辅助蛋白运输到内膜所必需的，允许快速的尿素依赖性细胞质和周质缓冲。ArsR的表达，而不是其磷酸化，是细菌生存力所必需的。本研究的目的是表征ArsS和ArsR在H. pyloritoacid.Materials and MethodsWild‐type H. pylori和anarsR（D52N）磷酸化缺陷菌株在酸性或中性pH下孵育。研究基因和蛋白表达、存活、脲酶蛋白的膜运输、脲酶活性和内部pH。ArsS驱动的尿素酶蛋白在酸中向膜的运输（恢复内部pH值所需）不依赖于ArsR磷酸化。ArsR磷酸化增加了尿素酶基因簇的表达，磷酸化缺陷突变体中负反馈的丧失导致总尿素酶activity.ConclusionsArsRS在酸驯化中具有双重功能：ArsS驱动的尿素酶在细胞质膜上向UreI运输的调节，以及ArsR磷酸化驱动的尿素酶基因簇表达的调节。ArsS和ArsR通过磷酸化依赖性和磷酸化非依赖性调节机制发挥作用，以影响酸适应并允许胃定植。进一步了解复杂的酸适应将影响未来的发展有针对性的，非抗生素治疗方案。
BackgroundThe pH‐sensitiveHelicobacter pyloriArsRS two‐component system (TCS) aids survival of this neutralophile in the gastric environment by directly sensing and responding to environmental acidity. ArsS is required for acid‐induced trafficking of urease and its accessory proteins to the inner membrane, allowing rapid, urea‐dependent cytoplasmic and periplasmic buffering. Expression of ArsR, but not its phosphorylation, is essential for bacterial viability. The aim of this study was to characterize the roles of ArsS and ArsR in the response ofH. pylorito acid.Materials and MethodsWild‐type H. pyloriand anarsR(D52N)phosphorylation‐deficient strain were incubated at acidic or neutral pH. Gene and protein expression, survival, membrane trafficking of urease proteins, urease activity, and internal pH were studied.ResultsPhosphorylation of ArsR is not required for acid survival. ArsS‐driven trafficking of urease proteins to the membrane in acid, required for recovery of internal pH, is independent of ArsR phosphorylation. ArsR phosphorylation increases expression of the urease gene cluster, and the loss of negative feedback in a phosphorylation‐deficient mutant leads to an increase in total urease activity.ConclusionsArsRS has a dual function in acid acclimation: regulation of urease trafficking to UreI at the cytoplasmic membrane, driven by ArsS, and regulation of urease gene cluster expression, driven by phosphorylation of ArsR. ArsS and ArsR work through phosphorylation‐dependent and phosphorylation‐independent regulatory mechanisms to impact acid acclimation and allow gastric colonization. Furthering understanding of the intricacies of acid acclimation will impact the future development of targeted, nonantibiotic treatment regimens.