Bearson B L, Wilson L, Foster J W
Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile 36688, USA.
J Bacteriol. 1998 May;180(9):2409-17. doi: 10.1128/JB.180.9.2409-2417.1998.
The acid tolerance response enables Salmonella typhimurium to survive exposures to potentially lethal acidic environments. The acid stress imposed in a typical assay for acid tolerance (log-phase cells in minimal glucose medium) was shown to comprise both inorganic (i.e., low pH) and organic acid components. A gene previously determined to affect acid tolerance, atbR, was identified as pgi, the gene encoding phosphoglucoisomerase. Mutations in pgi were shown to increase acid tolerance by preventing the synthesis of organic acids. Protocols designed to separate the stresses of inorganic from organic acids revealed that the regulators sigma38 (RpoS), Fur, and Ada have major effects on tolerance to organic acid stress but only minor effects on inorganic acid stress. In contrast, the two-component regulatory system PhoP (identified as acid shock protein ASP29) and PhoQ proved to be important for tolerance to inorganic [corrected] acid stress but had little effect against organic acid stress. PhoP mutants also failed to induce four ASPs, confirming a role for this regulator in acid tolerance. Acid shock induction of PhoP appears to occur at the transcriptional level and requires the PhoPQ system. Furthermore, induction by acid occurs even in the presence of high concentrations of magnesium, the ion known to be sensed by PhoQ. These results suggest that PhoQ can sense both Mg2+ and pH. Since phoP mutants are avirulent, the low pH activation of this system has important implications concerning the pathogenesis of S. typhimurium. The involvement of four regulators, two of which are implicated in virulence, underscores the complexity of the acid tolerance stress response and further suggests that features of acid tolerance and virulence are interwoven.
耐酸反应使鼠伤寒沙门氏菌能够在可能致死的酸性环境中存活。在典型的耐酸试验（在最低葡萄糖培养基中的对数期细胞）中施加的酸胁迫被证明包含无机（即低pH）和有机酸成分。先前确定影响耐酸性的基因atbR被鉴定为pgi，即编码磷酸葡萄糖异构酶的基因。pgi突变被证明通过阻止有机酸的合成来提高耐酸性。旨在分离无机酸和有机酸胁迫的实验方案表明，调节因子sigma38（RpoS）、Fur和Ada对有机酸胁迫耐受性有主要影响，但对无机酸胁迫影响较小。相比之下，双组分调节系统PhoP（被鉴定为酸休克蛋白ASP29）和PhoQ被证明对无机酸胁迫耐受性很重要，但对有机酸胁迫影响不大。PhoP突变体也未能诱导四种ASP，证实了该调节因子在耐酸性中的作用。PhoP的酸休克诱导似乎发生在转录水平，并且需要PhoPQ系统。此外，即使在存在高浓度镁（已知由PhoQ感知的离子）的情况下，酸也能诱导。这些结果表明PhoQ可以感知Mg2+和pH。由于phoP突变体无毒，该系统的低pH激活对鼠伤寒沙门氏菌的发病机制具有重要意义。四种调节因子的参与，其中两种与毒力有关，突出了耐酸应激反应的复杂性，并进一步表明耐酸性和毒力特征相互交织。
