Recognition of antimicrobial peptides by a bacterial sensor kinase.
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.
Bader
Martin W
MW
Department of Microbiology, University of Washington Medical School, 1959 NE Pacific Street, Seattle, Washington 98195, USA.
Sanowar
Sarah
S
Daley
Margaret E
ME
Schneider
Anna R
AR
Cho
Uhnsoo
U
Xu
Wenqing
W
Klevit
Rachel E
RE
Le Moual
Hervé
H
Miller
Samuel I
SI
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
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C079792:PhoQ protein, Bacteria; D011494:Protein Kinases; D008274:Magnesium