Identification of Streptococcus gallolyticus subsp. gallolyticus (Biotype I) Competence-Stimulating Peptide Pheromone

Streptococcus gallolyticus subsp.gallolyticus , a member of the group D streptococci, is normally found in the bovine rumen and human gut. It is an opportunistic pathogen that was recently determined to be a bacterial driver of colorectal cancer, in addition to causing other diseases, such as infective endocarditis, bacteremia, neonatal meningitis, and septicemia. As an emerging pathogen, not much is known about this bacterium, its virulence mechanisms, or its virulence regulatory pathways. Previous studies suggest thatS. gallolyticus subsp.gallolyticus uses a ComRS pathway, one of manyStreptococcus quorum-sensing circuitries, for competence. However, thus far, the ubiquitous ComABCDE pathway has not been studied, nor has its regulatory role inS. gallolyticus subsp.gallolyticus . We therefore sought to study theS. gallolyticus subsp.gallolyticus ComABCDE quorum-sensing pathway and have identified its peptide pheromone, which is termed the competence-stimulating peptide (CSP). We further determined that this peptide regulates the production of bacteriocin-like inhibitory substances (BLISs), a phenotype that has been linked with the ComABCDE pathway in bothStreptococcus pneumoniae andStreptococcus mutans . Our data show thatS. gallolyticus subsp.gallolyticus TX20005 produces a 21-mer CSP signal, which differs from CSP signals of otherStreptococcus species in that its active form begins three residues after the double-glycine leader signal of the ComC precursor peptide. Additionally, our data suggest that this peptide might not be related to competence induction, as opposed to CSP signaling peptides in otherStreptococcus species. This study provides the first evidence thatS. gallolyticus subsp.gallolyticus utilizes quorum sensing to eliminate competitors, presenting a potential pathway to target this emerging human pathogen.IMPORTANCE Streptococcus gallolyticus subsp.gallolyticus is an emerging human pathogen known as a causative agent of infective endocarditis, and recently, of colorectal cancer. In this work, we revealed a functional quorum-sensing circuitry inS. gallolyticus subsp.gallolyticus , including the identification of the central signaling peptide pheromone, competence-stimulating peptide (CSP), and the regulatory role of this circuitry in the production of bacteriocin-like inhibitory substances (BLISs). This work uncovered a mechanism by which this bacterium outcompetes other bacterial species and thus provides a potential tool to study this opportunistic pathogen.