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.