Evidence for complex interactions of stress-associated regulons in an mprAB deletion mutant of Mycobacterium tuberculosis
Evidence for complex interactions of stress-associated regulons in an mprAB deletion mutant of Mycobacterium tuberculosis
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DOI：
10.1099/mic.0.29281-0
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发表时间：
2007-04-01
期刊：
影响因子：
2.8
通讯作者：
Howard, Susan T.
中科院分区：
文献类型：
--
作者：
Pang, Xiuhua;Vu, Phong;Howard, Susan T.
二组分系统是细菌调控网络的重要组成部分。对结核分枝杆菌MprAB双组分系统作用的研究结果表明，它与几个应激反应调节因子有关。利用缺失反应调节因子MprA和组氨酸激酶MprB部分片段的缺失突变体，通过实时荧光定量聚合酶链式反应、引物延伸分析和DNA芯片分析，证明MprAB在小岛屿发展中国家的胁迫和指数生长过程中激活Sigma因子基因SiGe和SIGB。确定了mprA、SiGe和SIGB的依赖于MprA的SDS诱导转录起始点，这些点与MprA结合位点之间的距离的变化表明MprA参与了不同的启动子激活机制。虽然大部分SiGe调节子在缺失突变体中表达下调，但与单倍体生长相关的Rv1129c、Rv1130和Rv1131基因簇在SID胁迫下在缺失突变体中上调，这种上调依赖于大气生长条件。DosR、SigD和IDER等多种应激相关基因也在缺失突变体中上调，在指数生长和/或在SID存在的情况下。令人惊讶的是，与亲本菌株相比，缺失突变体对SID的抵抗力增强，并促进了人外周血单核细胞的生长，这些特征可能是由于失去了对应激相关基因的抑制。
Two-component systems are important constituents of bacterial regulatory networks. Results of this investigation into the role of the MprAB two-component system of Mycobacterium tuberculosis indicate that it is associated with the regulation of several stress-responsive regulons. Using a deletion mutant lacking portions of the response regulator, MprA, and the histidine kinase, MprB, it was demonstrated by real-time PCR, primer extension analyses and DNA microarrays that MprAB activates sigma factor genes sigE and sigB, under SIDS stress and during exponential growth. SDS-inducible, MprA-dependent transcriptional start points were identified for mprA, sigE and sigB, and variations in distance between these points and MprA-binding sites suggest that MprA is involved in different mechanisms of promoter activation. Although most of the SigE regulon was downregulated in the deletion mutant, the cluster of genes Rv1129c, Rv1130 and Rv1131, which is associated with growth in monoctyes, was upregulated in the deletion mutant under SIDS stress, and this upregulation was dependent upon atmospheric growth conditions. Multiple stress-associated genes of the DosR, SigD and IdeR regulons were also upregulated in the deletion mutant, during exponential growth and/or in the presence of SIDS. Surprisingly, the deletion mutant had increased resistance to SIDS compared to the parental strain, and enhanced growth in human peripheral blood monocytes, characteristics which may result from a loss of repression of stress-associated genes.