Affiliation:
1. Department of Chemistry, University of Nevada, Reno, Reno, Nevada, USA
Abstract
ABSTRACT
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 that
S. gallolyticus
subsp.
gallolyticus
uses a ComRS pathway, one of many
Streptococcus
quorum-sensing circuitries, for competence. However, thus far, the ubiquitous ComABCDE pathway has not been studied, nor has its regulatory role in
S. gallolyticus
subsp.
gallolyticus
. We therefore sought to study the
S. 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 both
Streptococcus pneumoniae
and
Streptococcus mutans
. Our data show that
S. gallolyticus
subsp.
gallolyticus
TX20005 produces a 21-mer CSP signal, which differs from CSP signals of other
Streptococcus
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 other
Streptococcus
species. This study provides the first evidence that
S. 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 in
S. 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.
Funder
HHS | NIH | National Institute of General Medical Sciences
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
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