Institute of Medical Microbiology, University of Zurich, Gloriastrasse 32, 8006 Zurich, Switzerland.
BMC Microbiol. 2012 Jan 24;12:17. doi: 10.1186/1471-2180-12-17.
The production of virulence factors in Staphylococcus aureus is tightly controlled by a complex web of interacting regulators. EsxA is one of the virulence factors that are excreted by the specialized, type VII-like Ess secretion system of S. aureus. The esxA gene is part of the σB-dependent SpoVG subregulon. However, the mode of action of SpoVG and its impact on other global regulators acting on esxA transcription is as yet unknown.
We demonstrate that the transcription of esxA is controlled by a regulatory cascade involving downstream σB-dependent regulatory elements, including the staphylococcal accessory regulator SarA, the ArlRS two-component system and SpoVG. The esxA gene, preceding the ess gene cluster, was shown to form a monocistronic transcript that is driven by a σA promoter, whereas a putative σB promoter identified upstream of the σA promoter was shown to be inactive. Transcription of esxA was strongly upregulated upon either sarA or sigB inactivation, but decreased in agr, arlR and spoVG single mutants, suggesting that agr, ArlR and SpoVG are able to increase esxA transcription and relieve the repressing effect of the σB-controlled SarA on esxA.
SpoVG is a σB-dependent element that fine-tunes the expression of esxA by counteracting the σB-induced repressing activity of the transcriptional regulator SarA and activates esxA transcription.
金黄色葡萄球菌中毒力因子的产生受到复杂的相互作用调控因子网络的严格控制。EsxA 是金黄色葡萄球菌特定的 VII 型样 Ess 分泌系统分泌的一种毒力因子。esxA 基因是依赖于 σB 的 SpoVG 亚调控子的一部分。然而，SpoVG 的作用模式及其对其他影响 esxA 转录的全局调控因子的影响尚不清楚。
我们证明，esxA 的转录受涉及下游依赖于 σB 的调控元件的调控级联控制，包括葡萄球菌辅助调节因子 SarA、ArlRS 双组分系统和 SpoVG。esxA 基因位于 ess 基因簇之前，被证明形成由 σA 启动子驱动的单顺反子转录本，而位于 σA 启动子上游的假定 σB 启动子被证明是无活性的。sarA 或 sigB 失活后，esxA 的转录被强烈上调，但在 agr、arlR 和 spoVG 单突变体中降低，表明 agr、ArlR 和 SpoVG 能够增加 esxA 的转录并减轻 σB 控制的转录调节因子 SarA 对 esxA 的抑制作用。
SpoVG 是一个依赖于 σB 的元件，通过抵消转录调节因子 SarA 诱导的 σB 抑制活性来精细调节 esxA 的表达，并激活 esxA 转录。
