Endopeptidase PepO Regulates the SpeB Cysteine Protease and Is Essential for the Virulence of Invasive M1T1 Streptococcus pyogenes.

摘要: Streptococcus pyogenes (group A [GAS]) causes a wide range of human infections. The pathogenesis GAS infections is dependent on the temporal expression numerous secreted and surface-associated virulence factors that interact with host proteins. Streptococcal pyrogenic exotoxin B (SpeB) one most extensively studied toxins produced by GAS, coordinate growth phase-dependent regulation speB linked to disease severity phenotypes. Here, we identified endopeptidase PepO as novel regulator SpeB in invasive M1 serotype strain 5448. By using transcriptomics followed quantitative reverse transcriptase PCR Western blot analyses, demonstrate through targeted mutagenesis influences induction gene expression. Compared wild-type complemented mutant strains, 5448ΔpepO more susceptible killing neutrophils attenuated murine model infection. Our results expand complex regulatory network operating control production suggest requirement during M1T1 5448 infections.IMPORTANCE Despite continuing susceptibility S. penicillin, this bacterial pathogen remains leading infectious cause global morbidity mortality. particular subclone (M1T1) has persisted globally for decades frequently isolated from patients noninvasive diseases countries. One key pathogenicity potent broad-spectrum cysteine protease SpeB. Although there been extensive research interest mechanisms expression, its genetic not fully understood. identify new disseminated clone being essential virulence.