CcpA Regulates Central Metabolism and Virulence Gene Expression in Streptococcus mutans
Open Access
- 1 April 2008
- journal article
- research article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 190 (7), 2340-2349
- https://doi.org/10.1128/jb.01237-07
Abstract
CcpA globally regulates transcription in response to carbohydrate availability in many gram-positive bacteria, but its role in Streptococcus mutans remains enigmatic. Using the fructan hydrolase ( fruA ) gene of S. mutans as a model, we demonstrated that CcpA plays a direct role in carbon catabolite repression (CCR). Subsequently, the expression of 170 genes was shown to be differently expressed (≥2-fold) in glucose-grown wild-type (UA159) and CcpA-deficient (TW1) strains ( P ≤ 0.001). However, there were differences in expression of only 96 genes between UA159 and TW1 when cells were cultivated with the poorly repressing substrate galactose. Interestingly, 90 genes were expressed differently in wild-type S. mutans when glucose- and galactose-grown cells were compared, but the expression of 515 genes was altered in the CcpA-deficient strain in a similar comparison. Overall, our results supported the hypothesis that CcpA has a major role in CCR and regulation of gene expression but revealed that in S. mutans there is a substantial CcpA-independent network that regulates gene expression in response to the carbohydrate source. Based on the genetic studies, biochemical and physiological experiments demonstrated that loss of CcpA impacts the ability of S. mutans to transport and grow on selected sugars. Also, the CcpA-deficient strain displayed an enhanced capacity to produce acid from intracellular stores of polysaccharides, could grow faster at pH 5.5, and could acidify the environment more rapidly and to a greater extent than the parental strain. Thus, CcpA directly modulates the pathogenic potential of S. mutans through global control of gene expression.Keywords
This publication has 54 references indexed in Scilit:
- Role of RelA of Streptococcus mutans in Global Control of Gene ExpressionJournal of Bacteriology, 2008
- Universal external RNA controls for microbial gene expression analysis using microarray and qRT-PCRJournal of Microbiological Methods, 2007
- Time-Resolved Determination of the CcpA Regulon of Lactococcus lactis subsp. cremoris MG1363Journal of Bacteriology, 2007
- The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurementsNature Biotechnology, 2006
- Different Roles of EIIAB Man and EII Glc in Regulation of Energy Metabolism, Biofilm Development, and Competence in Streptococcus mutansJournal of Bacteriology, 2006
- Staphylococcus aureus CcpA Affects Virulence Determinant Production and Antibiotic ResistanceAntimicrobial Agents and Chemotherapy, 2006
- Catabolite Control Protein A (CcpA) Contributes to Virulence and Regulation of Sugar Metabolism in Streptococcus pneumoniaeJournal of Bacteriology, 2005
- Galactose Metabolism by Streptococcus mutansApplied and Environmental Microbiology, 2004
- Analysis of cis- and trans- Acting Factors Involved in Regulation of the Streptococcus mutans Fructanase Gene ( fruA )Journal of Bacteriology, 2002
- Biochemical and genetic analysis of Streptococcus mutans -galactosidaseJournal of General Microbiology, 1991