Group A streptococcal myonecrosis: increased vimentin expression after skeletal-muscle injury mediates the binding of Streptococcus pyogenes.

Abstract

Necrotizing fasciitis and myonecrosis caused by invasive infection with group A streptococci (GAS) are life-threatening conditions that have reemerged worldwide. Half of all GAS myonecrosis cases have no known portal of entry; yet, for unknown reasons, infection becomes established precisely at the site of a prior, nonpenetrating minor injury, such as a muscle strain. We hypothesized that GAS establishes infection by binding to surface molecules that are up-regulated on injured skeletal-muscle cells. Here, we isolated and identified vimentin as the major skeletal-muscle GAS-binding protein. Furthermore, we found that vimentin expression was up-regulated on injured skeletal-muscle cells in vitro and was expressed in muscle tissues from a patient with GAS myonecrosis who died of streptococcal toxic shock syndrome. These findings provide a molecular mechanism to explain the development of severe GAS soft-tissue infections at the sites of prior minor muscle trauma. This understanding may provide a basis for novel preventive strategies or therapies for patients with this devastating infection.