Methicillin resistance and the biofilm phenotype in Staphylococcus aureus

Abstract

Antibiotic resistance and biofilm-forming capacity contribute to the success of Staphylococcus aureus as a human pathogen in both healthcare and community settings. These virulence factors do not function independently of each other and the biofilm phenotype expressed by clinical isolates of S. aureus is influenced by acquisition of the methicillin resistance gene mecA. Methicillin-sensitive S. aureus (MSSA) strains commonly produce an icaADBC operon-encoded polysaccharide intercellular adhesin (PIA)-dependent biofilm. In contrast, the release of extracellular DNA (eDNA) and cell surface expression of a number of sortase-anchored proteins, and the major autolysin have been implicated in the biofilm phenotype of methicillin-resistant S. aureus (MRSA) isolates. Expression of high level methicillin resistance in a laboratory MSSA strain resulted in (i) repression of PIA-mediated biofilm production, (ii) down-regulation of the accessory gene regulator (Agr) system, and (iii) attenuation of virulence in murine sepsis and device infection models. Here we review the mechanisms of MSSA and MRSA biofilm production and the relationships between antibiotic resistance, biofilm and virulence gene regulation in S. aureus.

Keywords: Atl; LPXTG proteins; PIA; Staphylococcus aureus; biofilm; c-di-AMP; mecA; methicillin resistance.

Figure 1

(A) Graphic representations of the biofilm phenotypes expressed by MSSA and MRSA. MSSA strains form ica-dependent, PIA-mediated biofilms whereas MRSA strains form biofilms independent of PIA and require surface proteins such as the fibronectin binding proteins, Atl-mediated cell lysis and eDNA for colonization of surfaces and biofilm accumulation. (B) Scanning electron micrographs (3500 × magnification) of biofilms formed by MSSA strain SH1000 grown in BHI media supplemented with 4% NaCl (left) and MRSA strain BH1CC grown in BHI supplemented with 1% glucose (right).