Is streptolysin S of group A streptococci a virulence factor?
The possible role played by streptolysin S (SLS) of group A streptococci in the pathophysiology of streptococcal infections and in post-streptococcal sequelae is discussed. The following properties of SLS justify its definition as a distinct virulence factor: 1) its presence on the streptococcus surface in a cell-bound form, 2) its continuous and prolonged synthesis by resting streptococci, 3) its non-immunogenicity, 4) its extractability by serum proteins (albumin, alpha lipoprotein), 5) its ability to become transferred directly to target cells while being protected from inhibitory agents in the milieu of inflammation, 6) its ability to bore holes in the membrane phospholipids in a large variety of mammalian cells, 7) its ability to synergize with oxidants, proteolytic enzymes, and with additional host-derived proinflammatory agonists, and 8) its absence in streptococcal mutants associated with a lower pathogenicity for animals. Because tissue damage in streptococcal and post-streptococcal sequelae might be the end result of a distinct synergism between streptococcal and host-derived proinflammatory agonists it is proposed that only cocktails of anti-inflammatory agents including distinct inhibitors of SLS (phospholipids), gamma globulin, inhibitors of reactive oxygen species, proteinases, cationic proteins cytokines etc., will be effective in inhibiting the multiple synergistic interactions which lead to fasciitis, myositis and the flesh-eating syndromes, and often develop into sepsis, septic shock and multiple organ failure. The creation of mutants deficient in SLS and in proteases will help shed light on the specific role played by SLS in the virulence of group A hemolytic streptococci.
Ginsburg
I
I
Department of Oral Biology, Hebrew University-Hadassah, Faculty of Dental Medicine founded by the Alpha-Omega Fraternity, Jerusalem, Israel. ginsburg@cc.huji.ac.il
D000818:Animals; D001426:Bacterial Proteins; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D004357:Drug Synergism; D010450:Endopeptidases / Q000008:administration & dosage / Q000633:toxicity; D019115:Fasciitis, Necrotizing / Q000209:etiology; D006801:Humans; D009154:Mutation; D016877:Oxidants / Q000008:administration & dosage / Q000633:toxicity; D012772:Shock, Septic / Q000209:etiology; D013290:Streptococcal Infections / Q000209:etiology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000472:pathogenicity*; D013301:Streptolysins / Q000008:administration & dosage / Q000235:genetics / Q000633:toxicity*; D014774:Virulence
D001426:Bacterial Proteins; D016877:Oxidants; D013301:Streptolysins; C026050:streptolysin S; D010450:Endopeptidases