Regulated expression of pathogen-associated molecular pattern molecules in Staphylococcus epidermidis: quorum-sensing determines pro-inflammatory capacity and production of phenol-soluble modulins.
Phenol-soluble modulin (PSM) is a peptide complex produced by the nosocomial pathogen Staphylococcus epidermidis that has a strong capacity to activate the human innate immune response. We developed a novel method based on liquid chromatography-mass spectrometry (LC-MS) to quantify the production of the individual PSM components. Each PSM peptide was abundant in most of the 76 S epidermidis strains tested. Importantly, none of the PSM components were secreted by an agr mutant strain, indicating that PSM synthesis is regulated strictly by the agr quorum-sensing system. Furthermore, the agr mutant strain failed to elicit production of TNFalpha by human myeloid cells and induced significantly less neutrophil chemotaxis compared with the wild-type strain. Thus, quorum-sensing in S. epidermidis dramatically influenced activation of human host defence. We propose that an agr quorum-sensing mechanism facilitates growth and survival in infected hosts by adapting production of the pro-inflammatory PSMs to the stage of infection.
Vuong
Cuong
C
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, 903 S 4th Street, Hamilton, MT 59840, USA.
Dürr
Manuela
M
Carmody
Aaron B
AB
Peschel
Andreas
A
Klebanoff
Seymour J
SJ
Otto
Michael
M
D001427:Bacterial Toxins / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity; D002853:Chromatography, Liquid; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D013058:Mass Spectrometry; D009154:Mutation; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000473:pathology; D013212:Staphylococcus epidermidis / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence
D001427:Bacterial Toxins; C025971:staphylococcal delta toxin