Institute of Molecular Systems Biology, Department of Biology, Eidgenössische Technische HochschuleZürich, Zürich 8093, Switzerland.
Institute of Molecular Systems Biology, Department of Biology, Eidgenössische Technische HochschuleZürich, Zürich 8093, Switzerland
Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9546-9553. doi: 10.1073/pnas.1920143117. Epub 2020 Apr 15.
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 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.
了解细菌如何在表面定殖以及如何响应细胞黏附来调节细胞周期的进展，这具有根本的重要性。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，揭示了表面感应如何通过第二信使环二鸟苷酸（c-di-GMP）将细胞接触与细胞周期起始偶联的分子机制。当菌毛丝缩回时，内膜中的单体菌毛库通过 PilA 的 17 个氨基酸跨膜螺旋被感知，从而激活 PleC-PleD 双组分信号系统，增加细胞内 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“起始细胞周期的菌毛”肽（CIP）。添加化学合成的 CIP 肽可启动细胞周期的进展，同时抑制表面附着。IV 型菌毛的广泛保守性及其在病原体中对宿主定植的重要性表明，CIP 肽模拟物提供了抑制表面感应、防止生物膜形成和控制持续性感染的策略。
