Donegan Niles P, Cheung Ambrose L
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA.
J Bacteriol. 2009 Apr;191(8):2795-805. doi: 10.1128/JB.01713-08. Epub 2009 Jan 30.
In Staphylococcus aureus, the sigB operon codes for the alternative sigma factor sigma(B) and its regulators that enable the bacteria to rapidly respond to environmental stresses via redirection of transcriptional priorities. However, a full model of sigma(B) regulation in S. aureus has not yet emerged. Earlier data has suggested that mazEF, a toxin-antitoxin (TA) module immediately upstream of the sigB operon, was transcribed with the sigB operon. Here we demonstrate that the promoter P(mazE) upstream of mazEF is essential for full sigma(B) activity and that instead of utilizing autorepression typical of TA systems, sigB downregulates this promoter, providing a negative-feedback loop for sigB to repress its own transcription. We have also found that the transcriptional regulator SarA binds and activates P(mazE). In addition, P(mazE) was shown to respond to environmental and antibiotic stresses in a way that provides an additional layer of control over sigB expression. The antibiotic response also appears to occur in two other TA systems in S. aureus, indicating a shared mechanism of regulation.
在金黄色葡萄球菌中，sigB操纵子编码替代西格玛因子西格玛（B）及其调节因子，使细菌能够通过重新调整转录优先级来快速响应环境压力。然而，金黄色葡萄球菌中西格玛（B）调节的完整模型尚未出现。早期数据表明，sigB操纵子上游紧邻的毒素-抗毒素（TA）模块mazEF与sigB操纵子一起转录。在此，我们证明mazEF上游的启动子P（mazE）对于完整的西格玛（B）活性至关重要，并且sigB不是利用TA系统典型的自我抑制，而是下调该启动子，为sigB抑制自身转录提供了一个负反馈环。我们还发现转录调节因子SarA结合并激活P（mazE）。此外，P（mazE）被证明以一种对sigB表达提供额外控制层的方式响应环境和抗生素压力。抗生素反应似乎也发生在金黄色葡萄球菌的另外两个TA系统中，表明存在一种共享的调节机制。
