Model summarizing secreted SpeB protease activity. (Left) In wild-type strains (approximately 85% of GAS strains cultured from infected humans), normal amounts of SpeB transcript are made (A), the enzymatically inactive zymogen (SpeBz) is translated and secreted through the ExPortal (B), and SpeBz is processed through multiple intra- and intermolecular steps to yield the potent broad-spectrum mature cysteine protease (SpeBm), which is a key virulence factor for human disease (C). (Right) A minority of GAS strains (15%) have a SpeB-deficient phenotype caused by mutations in genes implicated in transcription or posttranscriptional regulation (D), secretion (E), or posttranslational processing (F). SpeB-deficient strains constitute a minority among organisms causing either human invasive infections or pharyngitis (G).