Regulated expression of pathogen-associated molecular pattern molecules in Staphylococcus epidermidis: quorum-sensing determines pro-inflammatory capacity and production of phenol-soluble modulins

Abstract

SummaryPhenol-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 TNF a a a a 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.

Characterization of coagulase-negative staphylococci isolated from hospital indoor air and a comparative analysis between airborne and inpatient isolates of Staphylococcus epidermidis

“…There are some data that support the hypothesis that low agr activity induces biofilm formation (Otto & Götz, 2000;Vuong et al, 2004), whereas high agr activity increases the invasive capacity of S. epidermidis and the concomitant inhibition of biofilm (Vuong et al, 2004;Yao et al, 2005). However, our results did not corroborate this hypothesis, because 60 % of the strong biofilm producers among the total S. epidermidis isolates expressed RNAIII, whilst only 9 % of the weak and moderate producers showed an active agr operon.…”

A novel role for SarX in Staphylococcus epidermidis biofilm regulation

“…The S. aureus SarX protein has been implicated in the regulation of the agr system (Manna & Cheung, 2006), which is known to regulate biofilms in a strain-dependent manner (Beenken et al, 2003(Beenken et al, , 2010Boles & Horswill, 2008;Coelho et al, 2008;O'Neill et al, 2007;Regassa et al, 1992;Vuong et al, 2000aVuong et al, , b, 2003Vuong et al, , 2004. Here, real-time RT-PCR was employed to compare RNAIII transcription in overnight BHI glucose cultures of CSF41498 pLI50, CSF41498 pSESAX6, SARX1 pLI50 and SARX1 pSESAX6.…”

“…The accessory gene regulator (agr) system controls quorum sensing, and is known to influence the biofilm phenotype of staphylococci in a strain-dependent manner (Beenken et al, 2003(Beenken et al, , 2010Boles & Horswill, 2008;Coelho et al, 2008;O'Neill et al, 2007;Regassa et al, 1992;Vuong et al, 2000aVuong et al, , b, 2003Vuong et al, , 2004. The agr locus encodes two divergently transcribed mRNA transcripts, RNAII and RNAIII (Morfeldt et al, 1995;Novick & Geisinger, 2008).…”

“…Indeed, the agr locus is repressed in biofilms (Yarwood et al, 2004), and agrdeficient mutants can produce thicker biofilms from which detachment is impaired (Beenken et al, 2003;Vuong et al, 2003Vuong et al, , 2004Yarwood & Schlievert, 2000). Boles & Horswill (2008) demonstrated that adding exogenous AIP or depleting glucose activates the agr system and the production of extracellular proteases necessary for bacterial detachment (Boles & Horswill, 2008).…”

How Staphylococcus aureus biofilms develop their characteristic structure

“…They are genome-encoded and found in most staphylococcal strains, with a given species producing PSMs of usually only minor amino acid sequence similarity to PSMs of other species (16). Mutants in the quorum-sensing system Agr lack PSM production, because psm operon transcription is under strict control by the AgrA DNA binding protein (14,17,18). Most work on PSMs has been performed in S. epidermidis and S. aureus.…”