High‐frequency intracellular invasion of epithelial cells by serotype M1 group A streptococci: M1 protein‐mediated invasion and cytoskeletal rearrangements

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Abstract
A clonal variant of serotype M1 group A streptococcus (designated M1inv+) has been linked to severe and invasive infections, including sepsis, necrotizing fasciitis and toxic shock. High frequency internalization of cultured epithelial cells by the M1inv+ strain 90‐226 is dependent upon the M1 protein. Invasion of HeLa cells was blocked by an anti‐M1 antibody, invasion by an M1− strain (90‐226 emm1::km) was greatly reduced, and latex beads bound to M1 protein were readily internalized by HeLa cells. Beads coated with a truncated M1 protein were internalized far less frequently. Scanning electron microscopy indicated that streptococci invade by a zipper‐like mechanism, that may be mediated by interactions with host cell microvilli. Initially, internalized streptococci and streptococci undergoing endocytosis are associated with polymerized actin. Later in the internalization process, streptococcal‐containing vacuoles are associated with the lysosomal membrane glycoprotein, LAMP‐1.