CD44 as a receptor for colonization of the pharynx by group A Streptococcus

The pharynx is the primary reservoir for strains of group A Streptococcus ( GAS) associated both with pharyngitis (streptococcal sore throat) and with invasive or "flesh-eating" soft tissue infections. We now report that CD44, a hyaluronic acid-binding protein that mediates human cell-cell- and cell- extracellular matrix-binding interactions, functions as a receptor for GAS colonization of the pharynx in vivo. We found that attachment of GAS to mur ine epithelial keratinocytes was mediated by binding of the GAS hyaluronic acid capsular polysaccharide to CD44. In studies of transgenic mice with a selective defect in epithelial. expression of CD44, GAS adherence to CD44-d eficient keratinocytes in vitro was reduced compared with adherence to kera tinocytes expressing normal levels of CD44. After intranasal inoculation, G AS colonized the oropharynx of wild-type mice but failed to colonize transg enic mice deficient in CD44 expression. GAS colonization of wild-type mice could be blocked by coadministration of mAb to CD44 or by pretreatment of t he animals with exogenous hyaluronic acid. These results provide evidence t hat CD44 serves as a receptor for GAS colonization of the pharynx and suppo rt the potential efficacy of disrupting the interaction between the GAS hya luronic acid capsule and CD44 as a novel approach to preventing pharyngeal infection.