Metabolic intermediate acetyl phosphate modulates bacterial virulence via acetylation
Metabolic intermediate acetyl phosphate modulates bacterial virulence via acetylation
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代谢中间体乙酰磷酸通过乙酰化调节细菌毒力
DOI：
10.1080/22221751.2018.1558963
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发表时间：
2019
影响因子：
13.2
通讯作者：
Yao Yu-Feng
中科院分区：
文献类型：
--
作者：
Ren Jie;Sang Yu;Qin Ran;Su Yang;Cui Zhongli;Mang Zhiguo;Li Hao;Lu Shaoyong;Zhang Jian;Cheng Sen;Liu Xiaoyun;Li Jixi;Lu Jie;Wu Wenjuan;Zhao Guo-Ping;Shao Feng;Yao Yu-Feng
越来越多的证据表明，代谢在细菌毒力中起着重要作用。乙酰磷酸（AcP）是磷酸转乙酰酶-乙酸激酶途径的高能中间体，是大肠杆菌的主要乙酰供体。杆菌PhoP是细菌毒力所必需的转录因子。在这里，我们表明，在鼠伤寒沙门氏菌PhoP是非酶乙酰化的AcP，这改变了其转录活性，表明赖氨酸102（K102）的乙酰化是依赖于细胞内的AcP。K102的乙酰化水平在PhoP激活条件下降低，包括低镁、酸胁迫或吞噬作用后。值得注意的是，体外试验表明，K102乙酰化影响PhoP磷酸化并抑制其转录活性。细胞和小鼠模型都表明K102对沙门氏菌的毒力至关重要，并表明乙酰化参与调控PhoP活性。总之，目前的研究强调了代谢在细菌毒力中的重要性，并表明AcP可能是一个关键的介质。
ABSTRACT Accumulating evidence indicates that bacterial metabolism plays an important role in virulence. Acetyl phosphate (AcP), the high-energy intermediate of the phosphotransacetylase-acetate kinase pathway, is the major acetyl donor in E. coli. PhoP is an essential transcription factor for bacterial virulence. Here, we show in Salmonella typhimurium that PhoP is non-enzymatically acetylated by AcP, which modifies its transcriptional activity, demonstrating that the acetylation of Lysine 102 (K102) is dependent on the intracellular AcP. The acetylation level of K102 decreases under PhoP-activating conditions including low magnesium, acid stress or following phagocytosis. Notably, in vitro assays show that K102 acetylation affects PhoP phosphorylation and inhibits its transcriptional activity. Both cell and mouse models show that K102 is critical to Salmonella virulence, and suggest acetylation is involved in regulating PhoP activity. Together, the current study highlights the importance of the metabolism in bacterial virulence, and shows AcP might be a key mediator.