title: The response regulator ComE in Streptococcus mutans functions both as a transcription activator of mutacin production and repressor of CSP biosynthesis.
abstract: In Streptococcus pneumoniae, competence and bacteriocin genes are controlled by two two-component systems, ComED and BlpRH, respectively. In Streptococcus mutans, both functions are controlled by the ComED system. Recent studies in S. mutans revealed a potential ComE binding site characterized by two 11 bp direct repeats shared by each of the bacteriocin genes responsive to the competence-stimulating peptide (CSP). Interestingly, this sequence was not found in the upstream region of the CSP structural gene comC. Since comC is suggested to be part of a CSP-responsive and ComE-dependent autoregulatory loop, it was of interest to determine how it was possible that the ComED system could simultaneously regulate bacteriocin expression and natural competence. Using the intergenic region IGS1499, shared by the CSP-responsive bacteriocin nlmC and comC, it was demonstrated that both genes are likely to be regulated by a bifunctional ComE. In a comE null mutant, comC gene expression was increased similarly to a fully induced wild-type. In contrast, nlmC gene expression was nearly abolished. Deletion of ComD exerted a similar effect on both genes to that observed with the comE null mutation. Electrophoretic mobility shift assays (EMSAs) with purified ComE revealed specific shift patterns dependent on the presence of one or both direct repeats in the nlmC-comC promoter region. The two direct repeats were also required for the promoter activity of both nlmC and comC. These results suggest that gene regulation of comC in S. mutans is fundamentally different from that reported for S. pneumoniae, which implicates a unique regulatory mechanism that allows the coordination of bacteriocin production with competence development.
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA 90095, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Kreth
authors.affiliation: Division of Diagnostic Science, University of Southern California School of Dentistry, Los Angeles, CA.
authors.forename: David C I
authors.initials: DCI
authors.lastname: Hung
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA 90095, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Merritt
authors.affiliation: Dental Research Institute, University of Toronto, ON, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Perry
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA 90095, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Division of Diagnostic Science, University of Southern California School of Dentistry, Los Angeles, CA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Goodman
authors.affiliation: Dental Research Institute, University of Toronto, ON, Canada.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Cvitkovitch
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA 90095, USA.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shi
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA 90095, USA.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Qi
mesh_terms: D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D001430:Bacteriocins / Q000096:biosynthesis*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis; D021901:DNA, Intergenic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D017930:Genes, Reporter; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D012329:RNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013295:Streptococcus mutans / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D004269:DNA, Bacterial; D018076:DNA, Complementary; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C423628:competence factor, Streptococcus; C425769:mutacin IV; D008156:Luciferases