Pang Xiuhua, Vu Phong, Byrd Thomas F, Ghanny Saleena, Soteropoulos Patricia, Mukamolova Galina V, Wu Shiping, Samten Buka, Howard Susan T
Department of Microbiology and Immunology, Center for Pulmonary and Infectious Disease Control, University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Department of Medicine, Albuquerque Veterans Affairs Medical Center, 1501 San Pedro SE, Albuquerque, NM 87108, USA.
Microbiology (Reading). 2007 Apr;153(Pt 4):1229-1242. doi: 10.1099/mic.0.29281-0.
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 SDS 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 monocytes, was upregulated in the deletion mutant under SDS 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 SDS. Surprisingly, the deletion mutant had increased resistance to SDS 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.
双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，它与几种应激反应调节子的调控有关。利用缺失部分应答调节子MprA和组氨酸激酶MprB的缺失突变体，通过实时PCR、引物延伸分析和DNA微阵列证明，在SDS应激和指数生长期间，MprAB激活了σ因子基因sigE和sigB。确定了mprA、sigE和sigB的SDS诱导型、MprA依赖性转录起始点，这些点与MprA结合位点之间距离的变化表明MprA参与了不同的启动子激活机制。虽然缺失突变体中大多数SigE调节子被下调，但与单核细胞生长相关的基因簇Rv1129c、Rv1130和Rv1131在SDS应激下在缺失突变体中上调，且这种上调依赖于大气生长条件。DosR、SigD和IdeR调节子的多个应激相关基因在缺失突变体的指数生长期间和/或存在SDS时也上调。令人惊讶的是，与亲本菌株相比，缺失突变体对SDS的抗性增加，并且在人外周血单核细胞中的生长增强，这些特征可能是由于应激相关基因的抑制缺失所致。
