Molecular basis of Staphylococcus epidermidis infections

Abstract

Staphylococcus epidermidis is the most important member of the coagulase-negative staphylococci and one of the most abundant colonizers of human skin. While for a long time regarded as innocuous, it has been identified as the most frequent cause of device-related infections occurring in the hospital setting and is therefore now recognized as an important opportunistic pathogen. S. epidermidis produces a series of molecules that provide protection from host defenses. Specifically, many proteins and exopolymers, such as the exopolysaccharide PIA, contribute to biofilm formation and inhibit phagocytosis and the activity of human antimicrobial peptides. Furthermore, recent research has identified a family of pro-inflammatory peptides in S. epidermidis, the phenol-soluble modulins (PSMs), which have multiple functions in immune evasion and biofilm development, and may be cytolytic. However, in accordance with the relatively benign relationship that S. epidermidis has with its host, production of aggressive members of the PSM family is kept at a low level. Interestingly, in contrast to S. aureus with its large arsenal of toxins developed for causing infection in the human host, most if not all "virulence factors" of S. epidermidis appear to have original functions in the commensal lifestyle of this bacterium.

Fig. 1. The exopolysacharide PIA/PNAG

PIA/PNAG is a partially de-acetylated homopolymer of N-acetylglucosamine residues in β1–6 linkage (top right). It is synthesized by the gene products of the ica operon (bottom). Transcription of ica is under control of multiple global regulators and other regulatory influences (but not Agr). It also may be inactivated by insertion of IS256. IcaA and IcaD form a glucosaminyltransferase. IcaC likely functions as exporter of the growing PIA chain. IcaB de-acetylates pre-PIA at the cell surface after PIA export. Positive charges introduced by deacetylation are crucial for surface location and the multiple functions of PIA shown at the top left.

Fig. 2. Phenol-soluble modulins of S. epidermidis

A, Amino acid sequences of all S. epidermidis PSMs. PSMs are exported as the primary translation products with N-terminal N-formyl-methionine (fM). B, Genetic location of psm genes in the chromosome or in the case of psm-mec, on SCCmec elements. Gene numbers are according to the genome of ATCC12228. C, Roles of PSMs in inflammation, cytolysis, and biofilm development. All PSMs trigger inflammatory responses by interaction with the FPR2 receptor. PSMδ and to some extent, some other PSMs, function as cytolysins. PSMβ peptides and possibly other PSMs contribute to biofilm structuring and detachment.