Acetylation of PhoP K88 Is Involved in Regulating Salmonella Virulence
Acetylation of PhoP K88 Is Involved in Regulating Salmonella Virulence
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PhoP K88 的乙酰化参与调节沙门氏菌毒力
DOI：
10.1128/iai.00588-20
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发表时间：
2021-03-01
影响因子：
3.1
通讯作者：
Yao, Yu-Feng
中科院分区：
文献类型：
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作者：
Li, Jianhui;Liu, Shuting;Yao, Yu-Feng
鼠伤寒沙门氏菌的PhoP - PhoQ双组分调控系统参与对各种环境压力的响应，并且对细菌的毒力至关重要。我们之前的研究表明，乙酰化在调控PhoP的活性中起重要作用，从而介导鼠伤寒沙门氏菌毒力的变化。在此，我们证明一个保守的赖氨酸残基K88对PhoP的功能及其因乙酰化而下调的PhoP活性至关重要。K88可被乙酰磷酸（AcP）特异性乙酰化，并且在巨噬细胞吞噬鼠伤寒沙门氏菌后，K88的乙酰化水平显著降低。K88的乙酰化抑制PhoP的二聚化和DNA结合能力。此外，在小鼠模型中，将K88突变为谷氨酰胺（模拟乙酰化形式）可显著减轻鼠伤寒沙门氏菌引起的肠道炎症和全身感染。这些发现表明，AcP对PhoP的非酶促乙酰化是鼠伤寒沙门氏菌毒力的一种精细调节机制，并强调宿主中的毒力和代谢密切相关。
The PhoP-PhoQ two-component regulation system of Salmonella enterica serovar Typhimurium is involved in the response to various environmental stresses and is essential for bacterial virulence. Our previous studies showed that acetylation plays an important role in regulating the activity of PhoP, which consequently mediates the change in virulence of S. Typhimurium. ABSTRACT The PhoP-PhoQ two-component regulation system of Salmonella enterica serovar Typhimurium is involved in the response to various environmental stresses and is essential for bacterial virulence. Our previous studies showed that acetylation plays an important role in regulating the activity of PhoP, which consequently mediates the change in virulence of S. Typhimurium. Here, we demonstrate that a conserved lysine residue, K88, is crucial for the function of PhoP and its acetylation-downregulated PhoP activities. K88 could be specifically acetylated by acetyl phosphate (AcP), and the acetylation level of K88 decreased significantly after phagocytosis of S. Typhimurium by macrophages. Acetylation of K88 inhibited PhoP dimerization and DNA-binding abilities. In addition, mutation of K88 to glutamine, mimicking the acetylated form, dramatically attenuated intestinal inflammation and systemic infection of S. Typhimurium in the mouse model. These findings indicate that nonenzymatic acetylation of PhoP by AcP is a fine-tuned mechanism for the virulence of S. Typhimurium and highlights that virulence and metabolism in the host are closely linked.