Group A streptococcal myonecrosis: increased vimentin expression after skeletal-muscle injury mediates the binding of Streptococcus pyogenes.
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.
Bryant
Amy E
AE
Veterans Affairs Medical Center, Boise, Idaho 83702, USA. amy.bryant@mindspring.com
Bayer
Clifford R
CR
Huntington
Jeremy D
JD
Stevens
Dennis L
DL
D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D009336:Necrosis; D013290:Streptococcal Infections / Q000378:metabolism* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000502:physiology*; D014746:Vimentin / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
D014746:Vimentin