C-di-GMP Regulates Motile to Sessile Transition by Modulating MshA Pili Biogenesis and Near-Surface Motility Behavior in Vibrio cholerae.
C-di-GMP Regulates Motile to Sessile Transition by Modulating MshA Pili Biogenesis and Near-Surface Motility Behavior in Vibrio cholerae.
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DOI：
10.1371/journal.ppat.1005068
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发表时间：
2015-10
期刊：
影响因子：
6.7
通讯作者：
Yildiz FH
中科院分区：
文献类型：
--
作者：
Jones CJ;Utada A;Davis KR;Thongsomboon W;Zamorano Sanchez D;Banakar V;Cegelski L;Wong GC;Yildiz FH
在包括霍乱弧菌在内的许多细菌中，环二聚鸟苷一磷酸（c-di-GMP）控制着生物膜生活方式的转换。然而，很少有人知道这是如何发生的。在这项研究中，我们报告了c-di-GMP浓度的变化影响MshA皮利的生物合成，导致霍乱弧菌的运动性和生物膜表型改变。之前，我们报道了cdgJ编码c-di-GMP磷酸二酯酶，并且ΔcdgJ突变体具有降低的运动性和增强的生物膜形成。在这里，我们表明，甘露糖敏感的血凝素（MshA）菌毛生物发生所需的基因的损失恢复运动的ΔcdgJ突变体。预测的ATP酶蛋白mshE或pilT的突变，负责聚合和解聚MshA皮利，损害近表面运动行为和初始表面附着动力学。ΔcdgJ突变体具有增强的表面附着，而ΔcdgJmshA突变体表型模仿在ΔmshA菌株中观察到的高运动性和低附着表型。升高浓度的c-di-GMP增强表面MshA菌毛产生。MshE而不是PilT直接结合c-di-GMP，建立了MshA菌毛产生中c-di-GMP信号传导输入的机制。总的来说，我们的研究结果表明，由菌毛蛋白亚基的组装和拆卸建立的MshA菌毛的动态性质是必不可少的过渡从运动到固着的生活方式和C-二GMP影响MshA菌毛组装和功能，通过直接与MshE ATP酶的相互作用。人类病原体霍乱弧菌通过摄入受污染的食物和水引起使人衰弱的疾病霍乱。霍乱弧菌是水生环境中的天然居民。霍乱弧菌向人类宿主的传播依赖于病原体在水生水库中的存活，在水生水库中，它受到许多压力因素的挑战，包括环境理化参数的变化以及原生动物和寄生虫的捕食。一种用来忍受这些攻击的方法是形成一个多细胞群落，称为生物膜。信号分子环二聚鸟苷一磷酸（c-di-GMP）用于诱导许多细菌（包括霍乱弧菌）中的生物膜形成。我们证明，c-di-GMP促进生产的细胞表面结构称为MshA皮利结合分子马达负责聚合菌毛亚基。这些皮利是附着在表面上必不可少的粘性附属物。本研究确定了一种新的机制，c-di-GMP的菌毛生产通过相互作用的分子马达负责菌毛大会的调节。由于许多细菌利用皮利附着于表面，并利用c-di-GMP作为前生物膜信号分子，因此本文所述的菌毛调节和生物膜形成的机制可能在许多病原体中广泛存在。
In many bacteria, including Vibrio cholerae, cyclic dimeric guanosine monophosphate (c-di-GMP) controls the motile to biofilm life style switch. Yet, little is known about how this occurs. In this study, we report that changes in c-di-GMP concentration impact the biosynthesis of the MshA pili, resulting in altered motility and biofilm phenotypes in V. cholerae. Previously, we reported that cdgJ encodes a c-di-GMP phosphodiesterase and a ΔcdgJ mutant has reduced motility and enhanced biofilm formation. Here we show that loss of the genes required for the mannose-sensitive hemagglutinin (MshA) pilus biogenesis restores motility in the ΔcdgJ mutant. Mutations of the predicted ATPase proteins mshE or pilT, responsible for polymerizing and depolymerizing MshA pili, impair near surface motility behavior and initial surface attachment dynamics. A ΔcdgJ mutant has enhanced surface attachment, while the ΔcdgJmshA mutant phenocopies the high motility and low attachment phenotypes observed in a ΔmshA strain. Elevated concentrations of c-di-GMP enhance surface MshA pilus production. MshE, but not PilT binds c-di-GMP directly, establishing a mechanism for c-di-GMP signaling input in MshA pilus production. Collectively, our results suggest that the dynamic nature of the MshA pilus established by the assembly and disassembly of pilin subunits is essential for transition from the motile to sessile lifestyle and that c-di-GMP affects MshA pilus assembly and function through direct interactions with the MshE ATPase. The human pathogen Vibrio cholerae causes the debilitating disease cholera through ingestion of contaminated food and water. V. cholerae is a natural inhabitant of aquatic environments. Transmission of V. cholerae to the human host is dependent on survival of the pathogen in aquatic reservoirs where it is challenged with many stressors, including changes in the physiochemical parameters of environments and predation by protozoa and phages. One method utilized to endure these assaults is to form a multicellular community called a biofilm. The signaling molecule cyclic dimeric guanosine monophosphate (c-di-GMP) is utilized to induce biofilm formation in many bacteria, including V. cholerae. We demonstrate that c-di-GMP promotes the production of a cell surface structure called MshA pili by binding the molecular motor responsible for polymerizing pilus subunits. These pili are adhesive appendages that are essential for attachment to surfaces. This study identifies a novel mechanism for c-di-GMP regulation of pilus production through interactions with the molecular motor responsible for pilus assembly. Since many bacteria utilize pili for attachment to surfaces and c-di-GMP as a pro-biofilm signaling molecule, the mechanism for pilus regulation and biofilm formation described here may be widespread among many pathogens.