Role for a secreted cysteine proteinase in the establishment of host tissue tropism by group A streptococci

Primary infection of the human host by group A streptococci (GAS) most ofte n involves either the epidermis of the skin or the oropharyngeal mucosa. A humanized in vivo model for impetigo was used to investigate the basis for host tissue tropism among GAS. Disruption of the speB gene (encoding for a secreted cysteine proteinase) led to a loss of virulence for two impetigo-d erived strains (M-types 33 and 53), as evidenced by a diminution in tissue damage and a lack of reproductive growth. The level of cysteine proteinase activity in overnight cultures was associated with the extent of gross path ological changes induced by strains displaying varied degrees of virulence in the impetigo model. Moreover, high levels of secreted cysteine proteinas e activity correlated with a genetic marker for preferred tissue site of in fection at the skin (emm pattern D). The addition of exogenous SpeB to a sp eB mutant (emm pattern D) or to an avirulent throat-like strain (emm patter n A) led to increased bacterial reproduction at the skin. The data provide both experimental and epidemiological evidence for a critical role of a sec reted bacterial protease in promoting host tissue-specific infection.