EccA1, a Component of the Mycobacterium marinum ESX-1 Protein Virulence Factor Secretion Pathway, Regulates Mycolic Acid Lipid Synthesis
EccA1, a Component of the Mycobacterium marinum ESX-1 Protein Virulence Factor Secretion Pathway, Regulates Mycolic Acid Lipid Synthesis
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DOI：
10.1016/j.chembiol.2012.01.008
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发表时间：
2012-03-23
影响因子：
--
通讯作者：
Brown, Eric J.
中科院分区：
文献类型：
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作者：
Joshi, Shilpa A.;Ball, David A.;Brown, Eric J.
致病性分枝杆菌可引起包括结核病在内的多种疾病，通过ESX-1蛋白输出系统分泌疾病所必需的因子，并通过其富含脂质的细胞包膜部分保护其免受宿主防御。分枝杆菌生物学的这些致病特征被认为是相互独立的。ESX-1的关键组分包括三种ATP酶和EccA 1（海洋分枝杆菌MMAR_5443; M.结核病Rv 3868）是最不特征化的。在这里，我们表明，M。海洋EccA 1的ATP酶活性是ESX-1介导的蛋白质分泌所必需的，并且令人惊讶地是分枝菌酸（完整的细胞包膜脂质）的最佳合成所必需的。当EccA 1-ATP酶突变体在EccA 1-null菌株中表达时，观察到分枝菌酸合成缺陷增加，与体内毒力和细胞内生长降低相关。这些数据表明，两个分枝杆菌的毒力标志，ESX-1依赖的蛋白质分泌和分枝菌酸合成，是通过EccA 1密切相关。
Pathogenic mycobacteria, which cause multiple diseases including tuberculosis, secrete factors essential for disease via the ESX-1 protein export system and are partially protected from host defenses by their lipid-rich cell envelopes. These pathogenic features of mycobacterial biology are believed to act independently of each other. Key ESX-1 components include three ATPases, and EccA1 (Mycobacterium marinum MMAR_5443; M. tuberculosis Rv3868) is the least characterized. Here we show that M. marinum EccA1's ATPase activity is required for ESX-1-mediated protein secretion, and surprisingly for the optimal synthesis of mycolic acids, integral cell-envelope lipids. Increased mycolic acid synthesis defects, observed when an EccA1-ATPase mutant is expressed in an eccA1-null strain, correlate with decreased in vivo virulence and intracellular growth. These data suggest that two mycobacterial virulence hallmarks, ESX-1-dependent protein secretion and mycolic acid synthesis, are critically linked via EccA1.