Papenfort Kai, Silpe Justin E, Schramma Kelsey R, Cong Jian-Ping, Seyedsayamdost Mohammad R, Bassler Bonnie L
Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Department of Biology I, Ludwig-Maximilians University Munich, Martinsried, Germany.
Nat Chem Biol. 2017 May;13(5):551-557. doi: 10.1038/nchembio.2336. Epub 2017 Mar 20.
Quorum sensing (QS) is a cell-cell communication process that enables bacteria to track cell population density and orchestrate collective behaviors. QS relies on the production and detection of, and the response to, extracellular signal molecules called autoinducers. In Vibrio cholerae, multiple QS circuits control pathogenesis and biofilm formation. Here, we identify and characterize a new QS autoinducer-receptor pair. The autoinducer is 3,5-dimethylpyrazin-2-ol (DPO). DPO is made from threonine and alanine, and its synthesis depends on threonine dehydrogenase (Tdh). DPO binds to and activates a transcription factor, VqmA. The VqmA-DPO complex activates expression of vqmR, which encodes a small regulatory RNA. VqmR represses genes required for biofilm formation and toxin production. We propose that DPO allows V. cholerae to regulate collective behaviors to, among other possible roles, diversify its QS output during colonization of the human host.
群体感应(QS)是一种细胞间通讯过程,使细菌能够追踪细胞群体密度并协调集体行为。群体感应依赖于称为自诱导物的细胞外信号分子的产生、检测及对其的反应。在霍乱弧菌中,多个群体感应回路控制着发病机制和生物膜形成。在此,我们鉴定并表征了一对新的群体感应自诱导物-受体。该自诱导物是3,5-二甲基吡嗪-2-醇(DPO)。DPO由苏氨酸和丙氨酸合成,其合成依赖于苏氨酸脱氢酶(Tdh)。DPO结合并激活转录因子VqmA。VqmA-DPO复合物激活vqmR的表达,vqmR编码一种小调控RNA。VqmR抑制生物膜形成和毒素产生所需的基因。我们提出,DPO使霍乱弧菌能够调节集体行为,在人类宿主定殖期间发挥多种可能作用,包括使其群体感应输出多样化。