title: CovR-controlled global regulation of gene expression in Streptococcus mutans.
abstract: CovR/S is a two-component signal transduction system (TCS) that controls the expression of various virulence related genes in many streptococci. However, in the dental pathogen Streptococcus mutans, the response regulator CovR appears to be an orphan since the cognate sensor kinase CovS is absent. In this study, we explored the global transcriptional regulation by CovR in S. mutans. Comparison of the transcriptome profiles of the wild-type strain UA159 with its isogenic covR deleted strain IBS10 indicated that at least 128 genes (∼6.5% of the genome) were differentially regulated. Among these genes, 69 were down regulated, while 59 were up regulated in the IBS10 strain. The S. mutans CovR regulon included competence genes, virulence related genes, and genes encoded within two genomic islands (GI). Genes encoded by the GI TnSmu2 were found to be dramatically reduced in IBS10, while genes encoded by the GI TnSmu1 were up regulated in the mutant. The microarray data were further confirmed by real-time RT-PCR analyses. Furthermore, direct regulation of some of the differentially expressed genes was demonstrated by electrophoretic mobility shift assays using purified CovR protein. A proteomic study was also carried out that showed a general perturbation of protein expression in the mutant strain. Our results indicate that CovR truly plays a significant role in the regulation of several virulence related traits in this pathogenic streptococcus.
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dmitriev
authors.forename: Saswat S
authors.initials: SS
authors.lastname: Mohapatra
authors.forename: Patrick
authors.initials: P
authors.lastname: Chong
authors.forename: Melody
authors.initials: M
authors.lastname: Neely
authors.forename: Saswati
authors.initials: S
authors.lastname: Biswas
authors.forename: Indranil
authors.initials: I
authors.lastname: Biswas
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D024202:Electrophoretic Mobility Shift Assay; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D018085:Regulon / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013295:Streptococcus mutans / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins