Hyaluronic acid capsule and the role of streptococcal entry into keratinocytes in invasive skin infection.

It has been suggested that entry of pathogenic bacteria, including streptococci, into epithelial cells may represent an early stage of invasive infections. We found that poorly encapsulated wild-type strains and unencapsulated mutants of group A Streptococcus entered cultured human keratinocytes with high efficiency, while strains that produced large amounts of hyaluronic acid capsule did not, regardless of M-protein type or clinical source of the isolate. However, encapsulated streptococci produced extensive local necrosis and systemic infection in a mouse model of skin infection, while an isogenic acapsular strain did not. The results implicate the hyaluronic acid capsule as a virulence factor in soft tissue infection. Entry of poorly encapsulated group A Streptococcus into human epithelial cells does not appear to represent an initial step in invasive disease; rather, the capacity of encapsulated strains to avoid uptake by epithelial cells is associated with enhanced virulence in skin and soft tissue infection.