Bader Martin W, Sanowar Sarah, Daley Margaret E, Schneider Anna R, Cho Uhnsoo, Xu Wenqing, Klevit Rachel E, Le Moual Hervé, Miller Samuel I
Department of Microbiology, University of Washington Medical School, 1959 NE Pacific Street, Seattle, Washington 98195, USA.
Cell. 2005 Aug 12;122(3):461-72. doi: 10.1016/j.cell.2005.05.030.
PhoQ is a membrane bound sensor kinase important for the pathogenesis of a number of Gram-negative bacterial species. PhoQ and its cognate response regulator PhoP constitute a signal-transduction cascade that controls inducible resistance to host antimicrobial peptides. We show that enzymatic activity of Salmonella typhimurium PhoQ is directly activated by antimicrobial peptides. A highly acidic surface of the PhoQ sensor domain participates in both divalent-cation and antimicrobial-peptide binding as a first step in signal transduction across the bacterial membrane. Identification of PhoQ signaling mutants, binding studies with the PhoQ sensor domain, and structural analysis of this domain can be incorporated into a model in which antimicrobial peptides displace divalent cations from PhoQ metal binding sites to initiate signal transduction. Our findings reveal a molecular mechanism by which bacteria sense small innate immune molecules to initiate a transcriptional program that promotes bacterial virulence.
PhoQ是一种膜结合传感器激酶，对许多革兰氏阴性细菌物种的发病机制至关重要。PhoQ及其同源应答调节因子PhoP构成一个信号转导级联，控制对宿主抗菌肽的诱导抗性。我们发现鼠伤寒沙门氏菌PhoQ的酶活性直接被抗菌肽激活。PhoQ传感器结构域的高度酸性表面参与二价阳离子和抗菌肽的结合，作为跨细菌膜信号转导的第一步。PhoQ信号突变体的鉴定、与PhoQ传感器结构域的结合研究以及该结构域的结构分析可以纳入一个模型，其中抗菌肽从PhoQ金属结合位点取代二价阳离子以启动信号转导。我们的研究结果揭示了一种分子机制，细菌通过该机制感知小的先天免疫分子以启动促进细菌毒力的转录程序。
