A protein secretion pathway critical for Mycobacterium tuberculosis virulence is conserved and functional in Mycobacterium smegmatis

A protein secretion pathway critical for Mycobacterium tuberculosis virulence is conserved and functional in Mycobacterium smegmatis
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DOI:
10.1128/jb.187.4.1238-1245.2005
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发表时间:
2005-02-01
影响因子:
3.2
通讯作者:
Cox, JS
Cox, JS
中科院分区:
生物学3区
文献类型:
--
作者:
Converse, SE;Cox, JS

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Snm蛋白分泌系统是结核分枝杆菌毒力的关键决定因素。然而,编码该途径的基因在所有分枝杆菌中是保守的,包括非致病性的嗜盐性耻垢分枝杆菌。我们表明,Snm系统是可操作的M。耻垢病及其同源ESAT-6和CFP-10底物分泌受生长条件调节。更重要的是,我们发现M.嗜酸菌需要与M中分泌所需的基因同源的基因。结核采用基因敲除策略在M.除了smegegenerative,我们还发现了四个新的基因产物,是必不可少的Snm分泌,包括丝氨酸蛋白酶mycosin 1。尽管M.耻垢分枝杆菌和M.结核、M. Smn系统能分泌M.结核ESAT-6和CFP-10蛋白,表明底物识别也是保守的两个物种之间。M.因此,smeglobulin代表了一个强大的系统来研究多组分Snm分泌机器,并了解这个保守的系统在分枝杆菌生物学中的作用。
The Snm protein secretion system is a critical determinant of Mycobacterium tuberculosis virulence. However, genes encoding components of this pathway are conserved among all mycobacteria, including the nonpathogenic saprophyte Mycobacterium smegmatis. We show that the Snm system is operational in M. smegmatis and that secretion of its homologous ESAT-6 and CFP-10 substrates is regulated by growth conditions. Importantly, we show that Snm secretion in M. smegmatis requires genes that are homologous to those required for secretion in M. tuberculosis. Using a gene knockout strategy in M. smegmatis, we have also discovered four new gene products that are essential for Snm secretion, including the serine protease mycosin 1. Despite the evolutionary distance between M. smegmatis and M. tuberculosis, the M. smegmatis Smn system can secrete the M. tuberculosis ESAT-6 and CFP-10 proteins, suggesting that substrate recognition is also conserved between the two species. M. smegmatis, therefore, represents a powerful system to study the multicomponent Snm secretory machine and to understand the role of this conserved system in mycobacterial biology.