Post-transcriptional cross-talk between pro- and anti-colonization pili biosynthesis systems in Vibrio cholerae
Post-transcriptional cross-talk between pro- and anti-colonization pili biosynthesis systems in Vibrio cholerae
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DOI：
10.1111/j.1365-2958.2007.06091.x
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发表时间：
2008-02-01
影响因子：
3.6
通讯作者：
Zhu, Jun
中科院分区：
文献类型：
--
作者：
Hsiao, Ansel;Toscano, Kristin;Zhu, Jun
病原体霍乱弧菌调节许多基因的表达，以便从其环境储存库转变为人类宿主的生态位。其中包括编码两种相关的 IV 型菌毛的基因，即甘露糖敏感性血凝素 (MSHA) 菌毛，它有助于霍乱弧菌在水生环境中的持久存在，但会通过宿主免疫防御系统清除细菌，以及定植所需的毒素共调节菌毛 (TCP)。这些拮抗作用通过调节因子 ToxT 在转录上得到解决，该调节因子在感染过程中抑制 msh 基因，同时激活 tcp 基因。我们发现这两个药丸系统还通过 ToxT 调节的前菌毛蛋白肽酶 TcpJ 在转录后交织在一起。我们发现主要的 MSHA 菌毛蛋白 MshA 在霍乱弧菌中以 TcpJ 依赖性方式降解。在异源大肠杆菌系统中，TcpJ 可以识别 MshA 及其同源底物 TCP 亚基 TcpA，但 TcpJ 的处理会导致 MshA 降解。通过定点诱变和嵌合菌毛蛋白分析，我们表明该过程针对 MshA N 末端基序的组合，并依赖于 TcpJ 的蛋白水解活性。此外，tcpJ 的过度表达部分恢复了无法转录下调 msh 基因的细菌在幼年小鼠中定殖的能力。这些发现将协调蛋白水解描述为霍乱弧菌的一种调节机制，并说明了该生物体在面对剧烈环境变化时的适应性。
The pathogen Vibrio cholerae modulates the expression of many genes in order to transition from its environmental reservoir to its niche in the human host. Among these are genes encoding two related Type IV pili, the mannose-sensitive haemagglutinin (MSHA) pilus, which aids V cholerae persistence in aquatic environments but causes clearance of bacteria by host immune defences, and the toxin co-regulated pilus (TCP) required for colonization. These antagonistic effects are resolved transcriptionally by the regulator ToxT, which represses msh genes while activating tcp genes during infection. We show that these two pill systems are also intertwined post-transcriptionally through the ToxT-regulated pre-pilin peptidase TcpJ. We found that the major MSHA pilin, MshA, was degraded in V cholerae in a TcpJ-dependent fashion. In a heterologous Escherichia coli system, TcpJ can recognize both MshA and its cognate substrate, the TCP subunit TcpA, but that processing by TcpJ causes the degradation of MshA. Through site-directed mutagenesis and chimeric pilin analysis, we show that this process targets a combination of MshA N-terminal motifs and depends on the proteolytic activity of TcpJ. Moreover, overexpression of tcpJ partially restored the ability of bacteria unable to transcriptionally downregulate msh genes to colonize infant mice. These findings describe co-ordinated proteolysis as a regulatory mechanism in V cholerae and illustrate this organism's adaptability in the face of dramatic environmental changes.