title: The GlnR Regulon in Streptococcus mutans Is Differentially Regulated by GlnR and PmrA.
abstract: GlnR-mediated repression of the GlnR regulon at acidic pH is required for optimal acid tolerance in Streptococcus mutans, the etiologic agent for dental caries. Unlike most streptococci, the GlnR regulon is also regulated by newly identified PmrA (SMUGS5_RS05810) at the transcriptional level in S. mutans GS5. Results from gel mobility shift assays confirmed that both GlnR and PmrA recognized the putative GlnR box in the promoter regions of the GlnR regulon genes. By using a chemostat culture system, we found that PmrA activated the expression of the GlnR regulon at pH 7, and that this activation was enhanced by excess glucose. Deletion of pmrA (strain ΔPmrA) reduced the survival rate of S. mutans GS5 at pH 3 moderately, whereas the GlnR mutant (strain ΔGlnR) exhibited an acid-sensitive phenotype in the acid killing experiments. Elevated biofilm formation in both ΔGlnR and ΔPmrA mutant strains is likely a result of indirect regulation of the GlnR regulon since GlnR and PmrA regulate the regulon differently. Taken together, it is suggested that activation of the GlnR regulon by PmrA at pH 7 ensures adequate biosynthesis of amino acid precursor, whereas repression by GlnR at acidic pH allows greater ATP generation for acid tolerance. The tight regulation of the GlnR regulon in response to pH provides an advantage for S. mutans to better survive in its primary niche, the oral cavity.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Yi-Ywan M
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yueh-Ying
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jui-Lung
authors.initials: JL
authors.lastname: Hung
authors.affiliation: Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Pei-Min
authors.initials: PM
authors.lastname: Chen
authors.affiliation: Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jean-San
authors.initials: JS
authors.lastname: Chia
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites; D018441:Biofilms; D002241:Carbohydrates; D015964:Gene Expression Regulation, Bacterial; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D009154:Mutation; D011485:Protein Binding; D018085:Regulon / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013295:Streptococcus mutans / Q000235:genetics* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002241:Carbohydrates; D015534:Trans-Activators; C081902:pmrA protein, Bacteria