Mutually dependent secretion of proteins required for mycobacterial virulence
Mutually dependent secretion of proteins required for mycobacterial virulence
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DOI：
10.1073/pnas.0504922102
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发表时间：
2005-07-26
影响因子：
11.1
通讯作者：
Rubin, EJ
中科院分区：
文献类型：
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作者：
Fortune, SM;Jaeger, A;Rubin, EJ
ESX-1基因座是结核分枝杆菌完全毒力的关键区域，它编码两种分泌蛋白以及参与其分泌的其他基因。ESAT-6和CFP-10这两种蛋白质的分泌机制及其功能仍然未知。使用蛋白质组学的方法来寻找额外的蛋白质分泌的ESX-1基因座，我们发现，编码的蛋白质的染色体不连锁的基因，espA，也分泌的菌株含有ESX-1基因座，但不是由菌株与ESX-1缺失。发现单个ESX-1基因（包括编码ESAT-6和CFP-10的基因）的突变会阻断EspA分泌。令人惊讶的是，缺乏espA β的突变体不能分泌ESAT-6和CFP-10，并且在毒力测定中与ESX-1突变体一样减毒。结果表明，这些蛋白质的分泌，这是每一个致病性分枝杆菌的毒力的关键，是相互依赖的。结果进一步表明，辨别相互作用的性质和大分子复合物的结构将为蛋白质分泌的替代机制和分枝杆菌毒力提供见解。
The ESX-1 locus is a region critical for full virulence in Mycobacterium tuberculosis, which encodes two secreted proteins as well as other genes involved in their secretion. The mechanism of secretion of the two proteins, ESAT-6 and CFP-10, and their function remain unknown. Using proteomic methods to search for additional proteins secreted by the ESX-1 locus, we discovered that a protein encoded by a chromosomally unlinked gene, espA, is also secreted by strains that contain the ESX-1 locus but not by strains with ESX-1 deletions. Mutations in individual ESX-1 genes, including those that encode ESAT-6 and CFP-10, were found to block EspA secretion. Surprisingly, mutants that lack espA reciprocally failed to secrete ESAT-6 and CFP-10 and were as attenuated as ESX-1 mutants in virulence assays. The results indicate that secretion of these proteins, which are each critical for virulence of pathogenic mycobacteria, is mutually dependent. The results further suggest that discerning the nature of the interaction and the structure of macromolecular complexes will provide insights into both an alternative mechanism of protein secretion and mycobacterial virulence.