Core-Gene-Encoded Peptide Regulating Virulence-Associated Traits in Streptococcus mutans

Abstract

bRecently, high-coverage genome sequence of 57 isolates of Streptococcus mutans, the primary etiological agent of human dental caries, was completed. The SMU.1147 gene, encoding a 61-amino-acid (61-aa) peptide, was present in all sequenced strains of S. mutans but absent in all bacteria in current databases. Reverse transcription-PCR revealed that SMU.1147 is cotranscribed with scnK and scnR, which encode the histidine kinase and response regulator, respectively, of a two-component system (TCS). The C terminus of the SMU.1147 gene product was tagged with a FLAG epitope and shown to be expressed in S. mutans by Western blotting with an anti-FLAG antibody. A nonpolar mutant of SMU.1147 formed less biofilm in glucose-containing medium and grew slower than did the wild-type strain under aerobic and anaerobic conditions, at low pH, or in the presence of H 2 O 2 . Mutation of SMU.1147 dramatically reduced genetic competence and expression of comX and comY, compared to S. mutans UA159. The competence defect of the SMU.1147 mutant could not be overcome by addition of sigX-inducing peptide (XIP) in defined medium or by competence-stimulating peptide (CSP) in complex medium. Complementation with SMU.1147 on a plasmid restored all phenotypes. Interestingly, mutants lacking either one of the TCS components and a mutant lacking all three genes behaved like the wild-type strain for all phenotypes mentioned above, but all mutant strains grew slower than UA159 in medium supplemented with 0.3 M NaCl. Thus, the SMU.1147-encoded peptide affects virulence-related traits and dominantly controls quorum-sensing pathways for development of genetic competence in S. mutans.

A unique open reading frame within the comX gene of Streptococcus mutans regulates genetic competence and oxidative stress tolerance

“…Stress tolerance and the development of genetic competence in the dental pathogen S. mutans are intertwined to a remarkable degree (Senadheera et al ., ; Banu et al ., ; Okinaga et al ., ; Kajfasz et al ., ; Kim et al ., ; Guo et al ., ). One example of this integration is the heat shock‐inducible, surface‐associated serine protease HtrA that is induced by addition of CSP, while deletion of htrA results in decreased transformation efficiency (Ahn et al ., ).…”

“…Recent studies into multiple stress response pathways, such as VicRK (Senadheera et al ., ), HtrA (Ahn et al ., ), CiaRH (Ahn et al ., ), HdrMR (Okinaga et al ., ) and others (Merritt et al ., ; Abranches et al ., ; Banu et al ., ; Dmitriev et al ., ; Kajfasz et al ., ; Kim et al ., ) suggest there is strong overlap between the competence circuit and tolerance of environmental stressors. An additional operon, rcrRPQ , was recently characterized and appears to serve as a molecular link between (p)ppGpp metabolism, acid and oxidative stress tolerance, and genetic competence (Seaton et al ., ).…”

Morphological and proteomic analyses of the biofilms generated by Streptococcus mutans isolated from caries-active and caries-free adults

“…Similarly, it was reported in a previous study that inactivation of scnR in S. mutans caused no change in biofilm formation. 46 Transcription factors are a set of sophisticated proteins that could promote and regulate diverse metabolic processes. 47,48 In addition, different transcriptional regulators play different roles in biofilm formation.…”

Growth Phase and pH Influence Peptide Signaling for Competence Development in Streptococcus mutans

“…It is also not well understood how the ComRS and ComDE systems overlap to regulate competence gene expression or how the addition of XIP or CSP at high concentrations induces growth inhibition or cell death (23,24). Also of note, it was shown recently that the ability of the ComRS system to activate comX can be affected by a third peptide that influences competence through the TCS ScnRK (25).…”