State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
J Bacteriol. 2013 Mar;195(5):1022-30. doi: 10.1128/JB.01530-12. Epub 2012 Dec 21.
Yersinia pestis is one of the most dangerous bacterial pathogens. PhoP and cyclic AMP receptor protein (CRP) are global regulators of Y. pestis, and they control two distinct regulons that contain multiple virulence-related genes. The PhoP regulator and its cognate sensor PhoQ constitute a two-component regulatory system. The regulatory activity of CRP is triggered only by binding to its cofactor cAMP, which is synthesized from ATP by adenylyl cyclase (encoded by cyaA). However, the association between the two regulatory systems PhoP/PhoQ and CRP-cAMP is still not understood for Y. pestis. In the present work, the four consecutive genes YPO1635, phoP, phoQ, and YPO1632 were found to constitute an operon, YPO1635-phoPQ-YPO1632, transcribed as a single primary RNA, whereas the last three genes comprised another operon, phoPQ-YPO1632, transcribed with two adjacent transcriptional starts. Through direct PhoP-target promoter association, the transcription of these two operons was stimulated and repressed by PhoP, respectively; thus, both positive autoregulation and negative autoregulation of PhoP/PhoQ were detected. In addition, PhoP acted as a direct transcriptional activator of crp and cyaA. The translational/transcriptional start sites, promoter -10 and -35 elements, PhoP sites, and PhoP box-like sequences were determined for these PhoP-dependent genes, providing a map of the PhoP-target promoter interaction. The CRP and PhoP regulons have evolved to merge into a single regulatory cascade in Y. pestis because of the direct regulatory association between PhoP/PhoQ and CRP-cAMP.
鼠疫耶尔森菌是最危险的细菌病原体之一。 PhoP 和环磷酸腺苷受体蛋白 (CRP) 是鼠疫耶尔森菌的全局调节剂，它们控制着两个截然不同的调节子，其中包含多个与毒力相关的基因。 PhoP 调节剂及其同源传感器 PhoQ 构成了一个双组分调节系统。 CRP 的调节活性仅在与辅因子 cAMP 结合时被触发，cAMP 由腺苷酸环化酶（由 cyaA 编码）从 ATP 合成。然而， PhoP/PhoQ 和 CRP-cAMP 这两个调节系统之间的关联在鼠疫耶尔森菌中仍然不清楚。在本工作中，发现四个连续的基因 YPO1635、phoP、phoQ 和 YPO1632 构成了一个操纵子 YPO1635-phoPQ-YPO1632，转录为单个初级 RNA，而后三个基因构成了另一个操纵子 phoPQ-YPO1632，转录时有两个相邻的转录起始点。通过直接 PhoP 靶启动子关联，这两个操纵子的转录分别受到 PhoP 的刺激和抑制；因此，检测到 PhoP/PhoQ 的正自调节和负自调节。此外， PhoP 作为 crp 和 cyaA 的直接转录激活剂。确定了这些依赖 PhoP 的基因的翻译/转录起始位点、启动子-10 和-35 元件、PhoP 位点和 PhoP 盒样序列，提供了 PhoP 靶启动子相互作用的图谱。由于 PhoP/PhoQ 和 CRP-cAMP 之间的直接调节关联，CRP 和 PhoP 调节子已进化为融合为鼠疫耶尔森菌中的单个调节级联。
