title: Recognition of antimicrobial peptides by a bacterial sensor kinase.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Washington Medical School, 1959 NE Pacific Street, Seattle, Washington 98195, USA.
authors.forename: Martin W
authors.initials: MW
authors.lastname: Bader
authors.forename: Sarah
authors.initials: S
authors.lastname: Sanowar
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Daley
authors.forename: Anna R
authors.initials: AR
authors.lastname: Schneider
authors.forename: Uhnsoo
authors.initials: U
authors.lastname: Cho
authors.forename: Wenqing
authors.initials: W
authors.lastname: Xu
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Klevit
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Moual
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D000222:Adaptation, Physiological / Q000276:immunology; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D015964:Gene Expression Regulation, Bacterial; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D008274:Magnesium / Q000276:immunology; D008954:Models, Biological; D011485:Protein Binding; D011487:Protein Conformation; D011494:Protein Kinases / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C079792:PhoQ protein, Bacteria; D011494:Protein Kinases; D008274:Magnesium