Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Proteomics Laboratory, Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee, USA.
Infect Immun. 2021 Mar 17;89(4). doi: 10.1128/IAI.00597-20.
encounters a wide range of pH within the human stomach. In a comparison of cultured under neutral or acidic conditions, about 15% of genes are differentially expressed, and corresponding changes are detectable for many of the encoded proteins. The ArsRS two-component system (TCS), comprised of the sensor kinase ArsS and its cognate response regulator ArsR, has an important role in mediating pH-responsive changes in gene expression. In this study, we sought to delineate the pH-responsive ArsRS regulon and further define the role of ArsR in pH-responsive gene expression. We compared strains containing an intact ArsRS system with an null mutant or strains containing site-specific mutations of a conserved aspartate residue (D52) in ArsR, which is phosphorylated in response to signals relayed by the cognate sensor kinase ArsS. We identified 178 genes that were pH-responsive in strains containing an intact ArsRS system but not in Δ or mutants. These constituents of the pH-responsive ArsRS regulon include genes involved in acid acclimatization (, amidases), oxidative stress responses (, ), transcriptional regulation related to iron or nickel homeostasis (, ), and genes encoding outer membrane proteins (including , , , [], and ). When comparing strains containing an intact ArsRS TCS with mutants, each cultured at neutral pH, relatively few genes are differentially expressed. Collectively, these data suggest that ArsRS-mediated gene regulation has an important role in adaptation to changing pH conditions.
在人类胃中遇到广泛的 pH 值范围。在中性或酸性条件下培养的比较中，约 15%的基因表达差异，许多编码蛋白也可检测到相应的变化。 ArsRS 双组分系统（TCS）由感应激酶 ArsS 和其同源反应调节蛋白 ArsR 组成，在介导 pH 响应的基因表达变化方面起着重要作用。在这项研究中，我们试图描绘 pH 响应的 ArsRS 调控组，并进一步定义 ArsR 在 pH 响应基因表达中的作用。我们比较了含有完整 ArsRS 系统的菌株与 ArsR 缺失突变体或含有 ArsR 保守天冬氨酸残基（D52）特异性突变的菌株，该残基在感应激酶 ArsS 传递的信号作用下被磷酸化。我们鉴定了 178 个在含有完整 ArsRS 系统的菌株中 pH 响应的基因，但在Δ或突变体中没有。这些 pH 响应的 ArsRS 调控组的组成部分包括参与酸适应（，酰胺酶）、氧化应激反应（，）、与铁或镍稳态相关的转录调节（，）以及编码外膜蛋白的基因（包括，，，[]和）。当比较含有完整 ArsRS TCS 的菌株与突变体时，每个菌株都在中性 pH 下培养，差异表达的基因相对较少。总的来说，这些数据表明 ArsRS 介导的基因调控在适应不断变化的 pH 条件方面起着重要作用。
