Necrotizing Soft Tissue Infection Staphylococcus aureus but not S. pyogenes Isolates Display High Rates of Internalization and Cytotoxicity Toward Human Myoblasts

Background. Necrotizing soft tissue infections (NSTIs) caused by group A Streptococcus (GAS) and occasionally by Staphylococcus aureus (SA) frequently involve the deep fascia and often lead to muscle necrosis. Methods. To assess the pathogenicity of GAS and S. aureus for muscles in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA isolates were assessed in these cells. Bloodstream infections (BSI-SA) and noninvasive coagulase-negative staphylococci (CNS) isolates were used as controls. Results. NSTI-SA and BSI-SA exhibited stronger internalization into human keratinocytes and myoblasts than NSTI-GAS or CNS. S. aureus internalization reached over 30% in human myoblasts due to a higher percentage of infected myoblasts (>11%) as compared to keratinocytes (<3%). Higher cytotoxicity for myoblasts of NSTI-SA as compared to BSI-SA was attributed to higher levels of psma and RNAIII transcripts in NSTI-SA. However, the 2 groups were not discriminated at the genomic level. The cellular basis of high internalization rate in myoblasts was attributed to higher expression of alpha 5 beta 1 integrin in myoblasts. Major contribution of FnbpAB-integrin alpha 5 beta 1 pathway to internalization was confirmed by isogenic mutants. Conclusions. Our findings suggest a factor in NSTI-SA severity is the strong invasiveness of S. aureus in muscle cells, a property not shared by NSTI-GAS isolates.