Recognition of antimicrobial peptides by a bacterial sensor kinase

Cell 122: 461-472 (2005)

Speaker：楊朝傑                           Time：9/14/2005, 13:10~14:00

Commentator：何漣漪 老師                  Place：Room 601

Abstract：

Antimicrobial peptides are polypeptides with net positive charges and an important component of innate immunity.  It is believed that these cationic peptides interact directly with negatively charged biological membranes to kill the microorganism.  However, the bacteria have developed mechanisms to resist killing by antimicrobial peptides.  Resistance to antimicrobial peptides is typically acquired by modification of bacterial cell surface.  Cell surface lipid A modification of Gram-negative bacteria is regulated by a two-component system termed PhoPQ.  The PhoPQ system is a signal-transduction cascade composed of the membrane bound sensor kinase PhoQ and the cytosolic response regulator PhoP in Salmonella typhimurium.  The Salmonella PhoP/PhoQ system is activated in vivo within acidified macrophage phagosomes and repressed in vitro during bacterial growth in high concentrations of the divalent cations Ca²⁺, Mg²⁺, or Mn²⁺.  The authors’ previous work demonstrated that the PhoPQ system responds to sublethal concentration of antimicrobial peptides to promote resistance to peptide-mediated killing.¹  Nevertheless, the mechanism of PhoPQ activation is unclear.  In this paper, the authors found the PhoQ is directly activated by antimicrobial peptides.  Three independent approaches (binding studies, NMR structural analysis, and identification of PhoQ mutants) provide strong evidence that acidic surface of the PhoQ sensor domain is both for a divalent-cation and antimicrobial-peptide binding site.  According to these results, the authors proposed that the antimicrobial peptides could displace divalent cations from PhoQ sensor domain to initiate signal transduction.  These findings reveal a molecular mechanism by which bacteria sense small innate immune molecules to initiate a transcriptional program that promotes bacterial virulence.²

References：

1.      M. W. Bader et al. Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides. Mol. Microbiol. 50: 219–230 (2003).

2.      M. W. Bader et al. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 122: 461-472 (2005).