Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence.
Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence.
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细菌细胞质中的酸性pH传感是沙门氏菌毒力所必需的。
DOI：
10.1111/mmi.13439
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发表时间：
2016-09
影响因子：
3.6
通讯作者：
Groisman EA
中科院分区：
文献类型：
--
作者：
Choi J;Groisman EA
pH调节基因表达、生化活动和细胞行为。在兼性胞内致病菌肠沙门氏菌血清型鼠伤寒杆菌中，微酸性pH激活主毒力调控系统PhoP/PhoQ。传感器PhoQ包含一个参与信号感知的胞质外结构域，以及一个控制调节因子PhoP激活的胞质结构域。我们现在报道，令人惊讶的是，即使胞质外pH值保持中性，沙门氏菌自身胞质pH值的降低也会诱导phop激活基因的转录。PhoQ细胞质结构域的氨基酸替换阻碍了酸性pH的激活和小鼠的毒力减弱，但没有消除低Mg2+或抗菌肽C18G的激活。相反，PhoQ胞质外结构域的去除阻止了对PhoQ激活信号的响应，但对酸性pH没有影响。php依赖基因在非致病性s.b ongori中受到酸性pH的轻微诱导，但在致病性s.b enterica中受到低Mg2+和C18G的激活。我们的研究结果表明，PhoQ传感器使肠链球菌能够对宿主和细菌来源的信号做出反应，从而改变其细胞质pH值。
pH regulates gene expression, biochemical activities and cellular behaviors. A mildly acidic pH activates the master virulence regulatory system PhoP/PhoQ in the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. The sensor PhoQ harbors an extracytoplasmic domain implicated in signal sensing, and a cytoplasmic domain controlling activation of the regulator PhoP. We now report that, surprisingly, a decrease in Salmonella’s own cytoplasmic pH induces transcription of PhoP-activated genes even when the extracytoplasmic pH remains neutral. Amino acid substitutions in PhoQ’s cytoplasmic domain hindered activation by acidic pH and attenuated virulence in mice, but did not abolish activation by low Mg2+ or the antimicrobial peptide C18G. Conversely, removal of PhoQ’s extracytoplasmic domains prevented the response to the latter PhoQ-activating signals but not to acidic pH. PhoP-dependent genes were minimally induced by acidic pH in the non-pathogenic species S. bongori but were activated by low Mg2+ and C18G as in pathogenic S. enterica. Our findings indicate that the sensor PhoQ enables S. enterica to respond to both host- and bacterial-derived signals that alter its cytoplasmic pH.