The type IV pilin PilA couples surface attachment and cell-cycle initiation in Caulobacter crescentus
The type IV pilin PilA couples surface attachment and cell-cycle initiation in Caulobacter crescentus
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DOI：
10.1073/pnas.1920143117
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发表时间：
2020-04-28
影响因子：
11.1
通讯作者：
Christen, Beat
中科院分区：
文献类型：
--
作者：
Del Medico, Luca;Cerletti, Dario;Christen, Beat
了解细菌如何在表面定植并调节细胞周期进程以响应细胞粘附是至关重要的。在这里，我们使用转座子测序结合荧光共振能量转移（FRET）显微镜来揭示表面传感如何驱动月牙根杆菌细胞周期起始的分子机制。我们发现IV型毛蛋白PilA是主要的信号输入，通过第二信使环二gmp （c-二gmp）将表面接触偶联到细胞周期启动。当毛丝缩回时，毛蛋白的17个氨基酸跨膜螺旋感应到内膜中的单体毛蛋白库，激活PleC-PleD双组分信号系统，增加细胞c-di-GMP水平，并发出细胞周期开始的信号。我们将PilA信号序列命名为CIP，即“细胞周期启动pilin”肽。添加化学合成的CIP肽启动细胞周期进程，同时抑制表面附着。IV型菌毛的广泛保存及其在寄主定植病原体中的重要性表明，CIP肽模拟物提供了抑制表面传感、防止生物膜形成和控制持续感染的策略。
Understanding how bacteria colonize surfaces and regulate cell-cycle progression in response to cellular adhesion is of fundamental importance. Here, we use transposon sequencing in conjunction with fluorescence resonance energy transfer (FRET) microscopy to uncover the molecular mechanism for how surface sensing drives cell-cycle initiation in Caulobacter crescentus. We identify the type IV pilin protein PilA as the primary signaling input that couples surface contact to cell-cycle initiation via the second messenger cyclic di-GMP (c-di-GMP). Upon retraction of pili filaments, the monomeric pilin reservoir in the inner membrane is sensed by the 17-amino acid transmembrane helix of PilA to activate the PleC-PleD two-component signaling system, increase cellular c-di-GMP levels, and signal the onset of the cell cycle. We termed the PilA signaling sequence CIP for "cell-cycle initiating pilin" peptide. Addition of the chemically synthesized CIP peptide initiates cell-cycle progression and simultaneously inhibits surface attachment. The broad conservation of the type IV pili and their importance in pathogens for host colonization suggests that CIP peptide mimetics offer strategies to inhibit surface sensing, prevent biofilm formation and control persistent infections.