Delayed onset of systemic bacterial dissemination and subsequent death in mice injected intramuscularly with Streptococcus pyogenes strains

Streptococcus pyogenes causes severe invasive diseases in humans, including necrotizing fasciitis, sepsis, and streptococcal toxic shock syndrome (STS S). We found that mice infected intramuscularly (i.m.) with S. pyogenes str ains developed bacteremia and subsequent sudden death after at least 10 day s of a convalescent period. Mostly, it occurred more than 21 days after mus cle infection. We provisionally designate this phenomenon as "delayed death ." Just after muscle infection, all the mice lost weight and activity, but recovered completely within 3 days. They had kept good activity and a fine coat of fur till one or two days before their death. Some of the dead mice were found to have soft-tissue necrosis. There was no correlation between t he virulence leading to the delayed death and the severity of diseases from which strains were isolated. It was also found that the production of neit her streptococcal pyrogenic exotoxin (SPE) A nor B correlated to the virule nce leading to delayed death. The bacteria obtained from the organs of the mice with delayed death expressed capsule. We suggest that the mice with de layed onset of systemic bacterial dissemination and subsequent death after muscle infection with S. pyogenes are the animal models of STSS, because th e pathophysiology is extremely similar to that of human STSS.