High-frequency intracellular invasion of epithelial cells by serotype M1 group A streptococci: M1 protein-mediated invasion and cytoskeletal rearrangements.
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.
Department of Microbiology, University of Minnesota 55455, USA.
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PE
Dombek
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Cue
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J
Sedgewick
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Lam
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Ruschkowski
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Finlay
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Cleary
D000199:Actins / Q000032:analysis; D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000097:blood / Q000302:isolation & purification / Q000502:physiology; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood / Q000302:isolation & purification / Q000502:physiology; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000382:microbiology / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology; D004847:Epithelial Cells / Q000382:microbiology*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells / Q000382:microbiology / Q000648:ultrastructure; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D016296:Mutagenesis; D013297:Streptococcus pyogenes / Q000276:immunology / Q000472:pathogenicity*
D000199:Actins; D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein; C053476:invasin, Yersinia