Department of Microbial Pathogenesis, Yale School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Yale Microbial Sciences Institute, P.O. Box 27389, West Haven, CT 06516, USA.
Sci Signal. 2017 Aug 29;10(494):eaan6284. doi: 10.1126/scisignal.aan6284.
Acidic conditions, such as those inside phagosomes, stimulate the intracellular pathogen to activate virulence genes. The sensor PhoQ responds to a mildly acidic pH by phosphorylating, and thereby activating, the virulence regulator PhoP. This PhoP/PhoQ two-component system is conserved in a subset of Gram-negative bacteria. PhoQ is thought to be sufficient to activate PhoP in mildly acidic pH. However, we found that the -specific protein UgtL, which was horizontally acquired by before the divergence of and , was also necessary for PhoQ to activate PhoP under mildly acidic pH conditions but not for PhoQ to activate PhoP in response to low Mg or the antimicrobial peptide C18G. UgtL increased the abundance of phosphorylated PhoP by stimulating autophosphorylation of PhoQ, thereby increasing the amount of the phosphodonor for PhoP. Deletion of attenuated virulence and further reduced PhoP activation in a strain bearing a form of PhoQ that is not responsive to acidic pH. These data suggest that when experiences mildly acidic pH, PhoP activation requires PhoQ to detect pH and UgtL to amplify the PhoQ response. Our findings reveal how acquisition of a foreign gene can strengthen signal responsiveness in an ancestral regulatory system.
酸性条件，如吞噬体内部的酸性条件，会刺激细胞内病原体激活毒力基因。传感器 PhoQ 通过磷酸化来响应轻度酸性 pH 值，从而激活毒力调节因子 PhoP。这种 PhoP/PhoQ 双组分系统在一组革兰氏阴性细菌中是保守的。人们认为 PhoQ 足以在轻度酸性 pH 值下激活 PhoP。然而，我们发现，在 和 分化之前，通过水平基因转移获得的 UgtL 特异性蛋白，对于 PhoQ 在轻度酸性 pH 条件下激活 PhoP 也是必需的，但对于 PhoQ 响应低镁或抗菌肽 C18G 激活 PhoP 则不是必需的。UgtL 通过刺激 PhoQ 的自磷酸化来增加磷酸化 PhoP 的丰度，从而增加 PhoP 的磷酸供体数量。缺失 会减弱 的毒力，并进一步降低在一种对酸性 pH 无反应形式的 PhoQ 菌株中 PhoP 的激活。这些数据表明，当 经历轻度酸性 pH 值时，PhoP 激活需要 PhoQ 来检测 pH 值，并且需要 UgtL 来放大 PhoQ 的反应。我们的发现揭示了获得外源基因如何增强祖先调控系统的信号响应能力。
