Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins

Abstract

Summary Background Phenol-soluble modulins (PSMs) are amphipathic, pro-inflammatory proteins secreted by most Staphylococcus aureus isolates. This study tested the hypothesis that in vitro PSM production levels are associated with specific clinical phenotypes. Methods 177 methicillin-resistant S. aureus (MRSA) isolates from infective endocarditis (IE), skin and soft tissue infection (SSTI), and hospital-acquired/ventilator-associated pneumonia (HAP) were matched by geographic origin, then genotyped using spa-typing. In vitro PSM production was measured by high performance liquid chromatography/mass spectrometry. Statistical analysis was performed using Chi-squared or Kruskal–Wallis tests as appropriate. Results Spa type 1 was significantly more common in SSTI isolates (62.7% SSTI; 1.7% IE; 16.9% HAP; p < 0.0001) while HAP and IE isolates were more commonly spa type 2 (0% SSTI; 37.3% IE; 40.7% HAP; p < 0.0001). USA300 isolates produced the highest levels of PSMs in vitro. SSTI isolates produced significantly higher quantities of PSMα1-4, PSMβ1, and δ-toxin than other isolates (p < 0.001). These findings persisted when USA300 isolates were excluded from analysis.

Increased in vitro phenol-soluble modulin production is associated with soft tissue infection source in clinical isolates of methicillin-susceptible Staphylococcus aureus

“…PSMα peptides have also been shown to promote bacterial spread across surfaces (19), destroy neutrophils (5) and erythrocytes (20), and inhibit dendritic cell activity (21) that could potentiate detection by immune response on the skin. Clinically, MRSA isolates from patients with SSTI exhibited higher levels of PSM than MRSA from other distinct clinical syndromes (6). The current study extends this observation into MSSA isolates as well, and provides further evidence for a key role for PSM in the pathogenesis of SSTI.…”

“…Spa genotyping was performed as previously described (6, 17). The eGenomics online platform (http://tools.egenomics.com) was used to define spa type.…”

“…We previously showed that MRSA isolates from patients with SSTI produced significantly more PSMs in vitro than geographically-matched MRSA isolates from patients with either HAP or IE (6). However, our results could have been confounded by the presence of traits that were associated with the methicillin-resistance phenotype.…”

Characterization of the Pathogenicity of Streptococcus intermedius TYG1620 Isolated from a Human Brain Abscess Based on the Complete Genome Sequence with Transcriptome Analysis and Transposon Mutagenesis in a Murine Subcutaneous Abscess Model

“…4F). Recently, staphylococcal PSMs have been implicated in skin and soft tissue infection (SSTI) (28)(29)(30) and have shown significantly higher levels of expression in methicillin-resistant S. aureus (MRSA) strains isolated from SSTIs. These observations imply that the small ORFs detected in the present study might be candidates that contribute to in vivo abscess formation.…”

Community-Associated Meticillin Resistant Staphylococcus aureus: increased burden of infections in children and young people in Queensland and Australia

“…However, reports from mice models concluded that PVL is not a virulence determinant (62). Other reports have reported on the importance of other staphylococcal toxins / virulence determinants such as phenol soluble modulin alpha and alpha-haemolysin (Hla) (cytolytic toxins) (60,63,64). ST93, the Queensland clone is known to encode phenol soluble modulin alpha and alpha-haemolysin as well as PVL (49) and is virulent in animal infection models.…”