The signaling peptide SpoV regulates streptolysin O and enhances survival in murine blood.

(Group A , GAS) is a human pathogen that causes a wide range of diseases. For successful colonization within a variety of host niches, GAS must sense and respond to environmental changes. Intercellular communication mediated by peptides is one way GAS coordinates gene expression in response to diverse environmental stressors, which enhances bacterial survival and contributes to virulence. Using peptidomics we identified SpoV (treptococcal eptide cntrolling irulence) in culture supernatant fluids. SpoV is a secreted peptide encoded near the gene encoding the extracellular cholesterol-dependent cytolysin streptolysin O ( The addition of synthetic SpoV peptide derivatives, but not control peptides, increased transcript abundance in an M49 isolate but not in an M3 isolate. Deletion of decreased transcript abundance, extracellular SLO protein levels, and SLO-specific hemolytic activity. Complementation of the mutant increased transcript abundance. Lastly, a mutant was deficient in the ability to survive in murine blood compared to the parental strain. Moreover, pre-incubation of the mutant with synthetic SpoV peptide derivatives increased GAS survival. Our findings show that expression is regulated, in part, by the GAS-specific signaling peptide SpoV.GAS secretes signaling peptides that can alter gene expression and impact virulence. We used peptidomics to identify a signaling peptide designated SpoV. Further, we showed that SpoV altered the expression of the cholesterol-dependent cytolysin SLO. Peptide signaling plays an important regulatory role during disease progression among several bacterial pathogens, including GAS. The therapeutic potential of manipulating peptide-controlled regulatory networks is an attractive option for the development of novel therapeutic strategies that disrupt virulence gene expression.