The Pseudomonas aeruginosa sensor RetS switches Type III and Type VI secretion via c-di-GMP signalling
The Pseudomonas aeruginosa sensor RetS switches Type III and Type VI secretion via c-di-GMP signalling
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DOI：
10.1111/j.1462-2920.2011.02595.x
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发表时间：
2011-12-01
影响因子：
5.1
通讯作者：
Filloux, Alain
中科院分区：
文献类型：
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作者：
Moscoso, Joana A.;Mikkelsen, Helga;Filloux, Alain
急性细菌感染通过III型分泌系统（T3SS）与运动性和细胞毒性有关，而慢性感染与生物膜形成和毒性降低有关。在铜绿假单胞菌中，运动和不育之间的转变涉及包括RetS/GacS传感器在内的调控网络，以及第二信使c-di-GMP。RetS/GacS信号级联聚集在小rna RsmY和RsmZ上，它们通过RsmA控制一系列功能。ret突变诱导生物膜形成，高水平的c-二gmp产生类似的反应。在这项研究中，我们通过显示RetS突变体显示高水平的c-di-GMP，将RetS和c-di-GMP途径联系起来。此外，retS突变导致T3SS抑制，但也上调与慢性感染相关的VI型分泌系统（T6SS）。引人注目的是，T3SS和T6SS的产生可以通过人为调节c-二gmp水平来切换。我们发现二胍酸环化酶WspR特别参与T3SS/T6SS转换，而rsmi和RsmZ是c-di- gmp依赖性反应所必需的。这些结果提供了RetS/GacS和c-di-GMP途径之间的牢固联系，这些途径协调细菌的生活方式，以及决定铜绿假单胞菌感染策略的分泌系统。
Acute bacterial infections are associated with motility and cytotoxicity via the type III secretion system (T3SS), while chronic infections are linked to biofilm formation and reduced virulence. In Pseudomonas aeruginosa, the transition between motility and sessility involves regulatory networks including the RetS/GacS sensors, as well as the second messenger c-di-GMP. The RetS/GacS signalling cascade converges on small RNAs, RsmY and RsmZ, which control a range of functions via RsmA. A retS mutation induces biofilm formation, and high levels of c-di-GMP produce a similar response. In this study, we connect RetS and c-di-GMP pathways by showing that the retS mutant displays high levels of c-di-GMP. Furthermore, a retS mutation leads to repression of the T3SS, but also upregulates the type VI secretion system (T6SS), which is associated with chronic infections. Strikingly, production of the T3SS and T6SS can be switched by artificially modulating c-di-GMP levels. We show that the diguanylate cyclase WspR is specifically involved in the T3SS/T6SS switch and that RsmY and RsmZ are required for the c-di-GMP-dependent response. These results provide a firm link between the RetS/GacS and the c-di-GMP pathways, which coordinate bacterial lifestyles, as well as secretion systems that determine the infection strategy of P. aeruginosa.