Regulation of bacteriocin production and cell death by the VicRK signaling system in Streptococcus mutans.
The VicRK two-component signaling system modulates biofilm formation, genetic competence, and stress tolerance in Streptococcus mutans. We show here that the VicRK modulates bacteriocin production and cell viability, in part by direct modulation of competence-stimulating peptide (CSP) production in S. mutans. Global transcriptome and real-time transcriptional analysis of the VicK-deficient mutant (SmuvicK) revealed significant modulation of several bacteriocin-related loci, including nlmAB, nlmC, and nlmD (P < 0.001), suggesting a role for the VicRK in producing mutacins IV, V, and VI. Bacteriocin overlay assays revealed an altered ability of the vic mutants to kill related species. Since a well-conserved VicR binding site (TGTWAH-N(5)-TGTWAH) was identified within the comC coding region, we confirmed VicR binding to this sequence using DNA footprinting. Overexpression of the vic operon caused growth-phase-dependent repression of comC, comDE, and comX. In the vic mutants, transcription of nlmC/cipB encoding mutacin V, previously linked to CSP-dependent cell lysis, as well as expression of its putative immunity factor encoded by immB, were significantly affected relative to the wild type (P < 0.05). In contrast to previous reports that proposed a hyper-resistant phenotype for the VicK mutant in cell viability, the release of extracellular genomic DNA was significantly enhanced in SmuvicK (P < 0.05), likely as a result of increased autolysis compared with the parent. The drastic influence of VicRK on cell viability was also demonstrated using vic mutant biofilms. Taken together, we have identified a novel regulatory link between the VicRK and ComDE systems to modulate bacteriocin production and cell viability of S. mutans.
Dental Research Institute, University of Toronto, Toronto, Ontario, Canada.
D B
DB
Senadheera
M
M
Cordova
E A
EA
Ayala
L E
LE
Chávez de Paz
K
K
Singh
J S
JS
Downey
G
G
Svensäter
S D
SD
Goodman
D G
DG
Cvitkovitch
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001430:Bacteriocins / Q000096:biosynthesis*; D016923:Cell Death; D018983:DNA Footprinting; D004269:DNA, Bacterial / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013295:Streptococcus mutans / Q000502:physiology*
D001426:Bacterial Proteins; D001430:Bacteriocins; D004269:DNA, Bacterial; C119939:YycF protein, Bacteria; D011494:Protein Kinases; D000071677:Histidine Kinase