Bacillus anthracis sin Locus and Regulation of Secreted Proteases
Bacillus anthracis sin Locus and Regulation of Secreted Proteases
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DOI：
10.1128/jb.01083-10
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发表时间：
2011-02-01
影响因子：
3.2
通讯作者：
Koehler, Theresa M.
中科院分区：
文献类型：
--
作者：
Pflughoeft, Kathryn J.;Sumby, Paul;Koehler, Theresa M.
炭疽芽孢杆菌与非致病性枯草芽孢杆菌有许多相同的调控位点。其中一个基因座是sinIR，它在枯草芽孢杆菌中控制着产孢、生物膜的形成、运动和能力。由于已知炭疽芽孢杆菌不具有运动性、自然能力或不易形成生物膜，我们假设炭疽芽孢杆菌的sinIR调节与枯草芽孢杆菌不同。对炭疽芽孢杆菌亲本菌株和sinR突变菌株的全基因组表达芯片分析表明，炭疽芽孢杆菌和枯草芽孢杆菌的sinR调控具有有限的收敛性。炭疽芽孢杆菌的调控基因包括一些枯草芽孢杆菌sinr调控基因的同源物，包括sinIR位点附近的信号肽酶基因sipW和产孢基因spoIIE。炭疽芽孢杆菌SinR蛋白也能负调控蜡样芽孢杆菌群特有的sinIR位点附近基因的转录。这些基因包括calY和inhA1，它们是金属蛋白酶camelysin和免疫抑制剂A1 （inhA1）的结构基因，它们被认为分别与蜡样芽孢杆菌和炭疽芽孢杆菌的毒力有关。电泳迁移位移分析显示，炭疽芽孢杆菌的SinR直接结合了来自强调控基因（如calY和sipW）的启动子DNA，而不是与弱调控基因inhA1的启动子DNA。对sinR-、InhA1 -和caly -零突变体培养上清中camelysin和InhA1水平的评估表明，培养上清中InhA1的浓度与camelysin的浓度成反比。我们的数据与模型一致，其中InhA1蛋白酶水平在转录水平由SinR控制，在翻译后水平由camelysin控制。
Bacillus anthracis shares many regulatory loci with the nonpathogenic Bacillus species Bacillus subtilis. One such locus is sinIR, which in B. subtilis controls sporulation, biofilm formation, motility, and competency. As B. anthracis is not known to be motile, to be naturally competent, or to readily form biofilms, we hypothesized that the B. anthracis sinIR regulon is distinct from that of B. subtilis. A genome-wide expression microarray analysis of B. anthracis parental and sinR mutant strains indicated limited convergence of the B. anthracis and B. subtilis SinR regulons. The B. anthracis regulon includes homologues of some B. subtilis SinR-regulated genes, including the signal peptidase gene sipW near the sinIR locus and the sporulation gene spoIIE. The B. anthracis SinR protein also negatively regulates transcription of genes adjacent to the sinIR locus that are unique to the Bacillus cereus group species. These include calY and inhA1, structural genes for the metalloproteases camelysin and immune inhibitor A1 (InhA1), which have been suggested to be associated with virulence in B. cereus and B. anthracis, respectively. Electrophoretic mobility shift assays revealed direct binding of B. anthracis SinR to promoter DNA from strongly regulated genes, such as calY and sipW, but not to the weakly regulated inhA1 gene. Assessment of camelysin and InhA1 levels in culture supernates from sinR-, inhA1-, and calY-null mutants showed that the concentration of InhA1 in the culture supernatant is inversely proportional to the concentration of camelysin. Our data are consistent with a model in which InhA1 protease levels are controlled at the transcriptional level by SinR and at the posttranslational level by camelysin.