CcpA Regulates Central Metabolism and Virulence Gene Expression in Streptococcus mutans
Open accessAbstract
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The carbohydrate catabolite repression gene ccpA is located upstream of the S mutans bacteriocin production regulon and regulates its expression by controlling expression of S mutans competence stimulating peptide.
“The carbohydrate catabolite repression gene, catabolite control protein A (ccpA), is located upstream of the S mutans bacteriocin production regulon and has been shown to regulate the expression of this by controlling the expression of S mutans competence stimulating peptide.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [292]
Cites
MAQC Consortium, Shi, L., Shi, L., Reid, L. H., Jones, W. D., Shippy, R., Warrington, J. A., Baker, S. C., Collins, P. J., de Longueville, F., et al. (2006) · Nature Biotechnology · doi:10.1038/nbt1239 · Cited by 2,126 · see citing works
Biology, immunology, and cariogenicity of Streptococcus mutans
Hamada, S., & Slade, H. D. (1980) · Microbiological Reviews · doi:10.1128/mr.44.2.331-384.1980 · Cited by 1,907 · see citing works
Phosphoenolpyruvate:carbohydrate phosphotransferase systems of bacteria
Postma, P. W., Lengeler, J. W., & Jacobson, G. R. (1993) · Microbiological Reviews · doi:10.1128/mr.57.3.543-594.1993 · Cited by 1,802 · see citing works
Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen
Ajdić, D., McShan, W. M., McLaughlin, R. E., Savić, G., Chang, J. S., Carson, M. B., Primeaux, C., Tian, R., Kenton, S., Jia, H., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172501299 · Cited by 1,013 · see citing works
[57] Chloramphenicol acetyltransferase from chloramphenicol-resistant bacteria
Shaw, W. V. (1975) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(75)43141-x · Cited by 804 · see citing works
Brückner, R., & Titgemeyer, F. (2002) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2002.tb11123.x · Cited by 413 · see citing works
Deutscher, J., Küster-Schöck, E., Bergstedt, U., Charrier, V., & Hillen, W. (1995) · Molecular Microbiology · doi:10.1111/j.1365-2958.1995.tb02280.x · Cited by 365 · see citing works
Adaptation of Streptococcus mutans and Enterococcus hirae to acid stress in continuous culture
Belli, W. A., & Marquis, R. E. (1991) · Applied and Environmental Microbiology · doi:10.1128/aem.57.4.1134-1138.1991 · Cited by 312 · see citing works
Site-directed mutagenesis of a catabolite repression operator sequence in Bacillus subtilis.
Weickert, M. J., & Chambliss, G. H. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.16.6238 · Cited by 294 · see citing works
Oral Streptococci... Products of Their Environment
Burne, R. A. (1998) · Journal of Dental Research · doi:10.1177/00220345980770030301 · Cited by 267 · see citing works
Self-citationGlobal control of sugar metabolism: a Gram-positive solution
Titgemeyer, F., & Hillen, W. (2002) · Antonie van Leeuwenhoek · doi:10.1023/a:1020628909429 · Cited by 238 · see citing works
Stülke, J., Arnaud, M., Rapoport, G., & Martin‐Verstraete, I. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.00839.x · Cited by 231 · see citing works
Responses of Cariogenic Streptococci to Environmental Stresses
Lemos, J. A. C., Abranches, J., & Burne, R. A. (2005) · Current Issues in Molecular Biology · doi:10.21775/cimb.007.095 · Cited by 221 · see citing works
Self-citationBacterial phosphotransferase system (PTS) in carbohydrate uptake and control of carbon metabolism
Kotrba, P., Inui, M., & Yukawa, H. (2001) · Journal of Bioscience and Bioengineering · doi:10.1016/s1389-1723(01)80308-x · Cited by 218 · see citing works
Staphylococcus aureus CcpA Affects Virulence Determinant Production and Antibiotic Resistance
Seidl, K., Stucki, M., Ruegg, M., Goerke, C., Wolz, C., Harris, L. G., Berger‐Bächi, B., & Bischoff, M. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.50.4.1183-1194.2006 · Cited by 213 · see citing works
Global analysis of carbohydrate utilization by Lactobacillus acidophilus using cDNA microarrays
Barrangou, R., Azcárate-Peril, M. A., Duong, T., Conners, S. B., Kelly, R. M., & Klaenhammer, T. R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511287103 · Cited by 200 · see citing works
Iyer, R., Baliga, N. S., & Camilli, A. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.24.8340-8349.2005 · Cited by 186 · see citing works
The role of the CcpA transcriptional regulator in carbon metabolism inBacillus subtilis
Henkin, T. M. (1996) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1996.tb07959.x · Cited by 181 · see citing works
[127] The use of starch electrophoresis in dehydrogenase studies
Fine, I. H., & Costello, L. A. (1963) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(63)06267-4 · Cited by 175 · see citing works
Porphyromonas gingivicanis sp. nov. and Porphyromonas crevioricanis sp. nov., Isolated from Beagles
Hirasawa, M., & Takada, K. (1994) · International Journal of Systematic Bacteriology · doi:10.1099/00207713-44-4-637 · Cited by 157 · see citing works
Time-Resolved Determination of the CcpA Regulon of Lactococcus lactis subsp. cremoris MG1363
Zomer, A., Buist, G., Larsen, R., Kok, J., & Kuipers, O. P. (2007) · Journal of Bacteriology · doi:10.1128/jb.01013-06 · Cited by 156 · see citing works
Abranches, J., Candella, M. M., Wen, Z. T., Baker, H. V., & Burne, R. A. (2006) · Journal of Bacteriology · doi:10.1128/jb.00169-06 · Cited by 151 · see citing works
Self-citationGriswold, A. R., Jameson‐Lee, M., & Burne, R. A. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.3.834-841.2006 · Cited by 142 · see citing works
Self-citationExpression, purification, and characterization of an exo-beta-D-fructosidase of Streptococcus mutans
Burne, R. A., Schilling, K., Bowen, W. H., & Yasbin, R. E. (1987) · Journal of Bacteriology · doi:10.1128/jb.169.10.4507-4517.1987 · Cited by 131 · see citing works
Self-citationBurne, R. A., Wen, Z. T., Chen, Y. M., et al. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.9.2863-2871.1999 · Cited by 130 · see citing works
Self-citationClarkson, L. A., & Crawford, M. (2001) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780198227519.001.0001 · Cited by 117 · see citing works
Catabolite Repression and Activation in Bacillus subtilis : Dependency on CcpA, HPr, and HprK
Lorca, G. L., Chung, Y. J., Barabote, R. D., WEYLER, W. J., Schilling, C. H., & Saier, M. H. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.22.7826-7839.2005 · Cited by 106 · see citing works
Influence of the Lactose Plasmid on the Metabolism of Galactose by Streptococcus lactis
LeBlanc, D. J., Crow, V. L., Lee, L. N., et al. (1979) · Journal of Bacteriology · doi:10.1128/jb.137.2.878-884.1979 · Cited by 97 · see citing works
Varga, J. J., Stirewalt, V. L., & Melville, S. B. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.16.5221-5229.2004 · Cited by 96 · see citing works
Abranches, J., Chen, Y. M., & Burne, R. A. (2003) · Applied and Environmental Microbiology · doi:10.1128/aem.69.8.4760-4769.2003 · Cited by 92 · see citing works
Self-citationCyclic AMP-independent catabolite repression in bacteria
Saier, M. H. (1996) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1996.tb08141.x · Cited by 90 · see citing works
Burne, R. A., Chen, Y.-Y. M., Wexler, D. L., Kuramitsu, H., & Bowen, W. H. (1996) · Journal of Dental Research · doi:10.1177/00220345960750080801 · Cited by 89 · see citing works
Self-citationAdaptive Acid Tolerance Response of Streptococcus sobrinus
Nascimento, M. M., Lemos, J. A. C., Abranches, J., Gonçalves, R. B., & Burne, R. A. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.19.6383-6390.2004 · Cited by 81 · see citing works
Self-citationZeng, L., Wen, Z. T., & Burne, R. A. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05359.x · Cited by 79 · see citing works
Self-citationMartin‐Verstraete, I., Deutscher, J., & Galinier, A. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.9.2966-2969.1999 · Cited by 70 · see citing works
Spatafora, G. A., Rohrer, K., Barnard, D., & Michalek, S. M. (1995) · Infection and Immunity · doi:10.1128/iai.63.7.2556-2563.1995 · Cited by 69 · see citing works
Role of RelA of Streptococcus mutans in Global Control of Gene Expression
Nascimento, M. M., Lemos, J. A. C., Abranches, J., Lin, V. K., & Burne, R. A. (2007) · Journal of Bacteriology · doi:10.1128/jb.01395-07 · Cited by 65 · see citing works
Self-citationGalactose Metabolism by Streptococcus mutans
Abranches, J., Chen, Y. M., & Burne, R. A. (2004) · Applied and Environmental Microbiology · doi:10.1128/aem.70.10.6047-6052.2004 · Cited by 61 · see citing works
Self-citationIdentification of a Homolog of CcpA Catabolite Repressor Protein in Streptococcus mutans
Simpson, C. L., & Russell, R. R. B. (1998) · Infection and Immunity · doi:10.1128/iai.66.5.2085-2092.1998 · Cited by 58 · see citing works
Universal external RNA controls for microbial gene expression analysis using microarray and qRT-PCR
Liu, Z. L., & Slininger, P. J. (2006) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2006.10.014 · Cited by 55 · see citing works
CcpB, a Novel Transcription Factor Implicated in Catabolite Repression in Bacillus subtilis
Chauvaux, S., Paulsen, I. T., & Saier, M. H. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.3.491-497.1998 · Cited by 55 · see citing works
Vadeboncoeur, C., Brochu, D., & Reizer, J. (1991) · Analytical Biochemistry · doi:10.1016/0003-2697(91)90112-7 · Cited by 53 · see citing works
Spatafora, G. A., Sheets, M., June, R., Luyimbazi, D. T., Howard, K., Hulbert, R. R., Barnard, D., el Janne, M., & Hudson, M. C. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.8.2363-2372.1999 · Cited by 49 · see citing works
Mechanism of Repression by Bacillus subtilis CcpC, a LysR Family Regulator
Kim, S., Jourlin‐Castelli, C., Wellington, S., & Sonenshein, A. L. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.09.078 · Cited by 44 · see citing works
Biochemical and genetic analysis of Streptococcus mutans -galactosidase
Aduse‐Opoku, J., Tao, L., & Ferretti, J. J. (1991) · Journal of General Microbiology · doi:10.1099/00221287-137-9-2271 · Cited by 42 · see citing works
Wen, Z. T., & Burne, R. A. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.1.126-133.2002 · Cited by 41 · see citing works
Self-citationZeng, L., Dong, Y., & Burne, R. A. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.3.941-949.2006 · Cited by 40 · see citing works
Self-citationBiochemical and genetic analysis of Streptococcus mutans -galactosidase
Aduse‐Opoku, J., Tao, L., Ferretti, J. J., et al. (1991) · Journal of General Microbiology · doi:10.1099/00221287-137-4-757 · Cited by 36 · see citing works
Wen, Z. T., Browngardt, C. M., & Burne, R. A. (2001) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2001.tb10969.x · Cited by 34 · see citing works
Self-citationBrowngardt, C. M., Wen, Z. T., & Burne, R. A. (2004) · FEMS Microbiology Letters · doi:10.1016/j.femsle.2004.09.012 · Cited by 32 · see citing works
Self-citationcis-Acting elements that regulate the low-pH-inducible urease operon of Streptococcus salivarius
Chen, Y. M., Betzenhauser, M. J., & Burne, R. A. (2002) · Microbiology · doi:10.1099/00221287-148-11-3599 · Cited by 32 · see citing works
Self-citationOsmotic stress responses ofStreptococcus mutansUA159
Abranches, J., Lemos, J. A. C., & Burne, R. A. (2006) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2005.00076.x · Cited by 30 · see citing works
Self-citationVadeboncoeur, C., & Gauthier, L. (1987) · Canadian Journal of Microbiology · doi:10.1139/m87-020 · Cited by 20 · see citing works
CcpA-independent carbon catabolite repression in Bacillus subtilis.
Dahl, M. K. (2002) · PubMed · Cited by 19 · see citing works
Recent advances in defining the cariogenicity of mutans streptococci: Molecular genetic approaches
Kuramitsu, H. K. (1987) · European Journal of Epidemiology · doi:10.1007/bf00149733 · Cited by 14 · see citing works
Diagnosis of hemoglobinopathies by high-performance liquid chromatography
Ou, C. (1997) · Journal of Biomedical Science · doi:10.1007/bf02258356 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The oral microbiome: Role of key organisms and complex networks in oral health and disease
Sedghi, L., DiMassa, V., Harrington, A., Lynch, S. V., & Kapila, Y. L. (2021) · Periodontology 2000 · doi:10.1111/prd.12393 · Cited by 755 · see citing works
Moye, Z. D., Zeng, L., & Burne, R. A. (2014) · Journal of Oral Microbiology · doi:10.3402/jom.v6.24878 · Cited by 164 · see citing works
“mutans clearly show a critical role for this regulator in direct and indirect control of transcription of genes that encode products involved in carbon flow, energy metabolism, and the fate of pyruvate (29).”
BackgroundResult
- Authors
- Abranches, J., Nascimento, M. M., Zeng, L., Browngardt, C. M., Wen, Z. T., Rivera, M. F., & Burne, R. A.
- Affiliations
- University of Florida Health (US)
- University of Florida (US)
- Corresponding author
- Burne, Robert A.
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2008-04
- Volume
- 190
- Issue
- 7
- Pages
- 2340-2349
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC2293215
- OpenAlex
- W2132219663
- Cited by
- 147
- References
- 56
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 4 · 2019: 11 · 2018: 11 · 2017: 3 · 2016: 9 · 2015: 7 · 2014: 13 · 2013: 10 · 2012: 8
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Bacteriology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Dental and Craniofacial Research (DE12236, R01DE012236)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
- Keywords
- California Consumer Privacy Act, Streptococcus mutans, catabolite repression, transcriptional regulation, virulence gene expression, central carbon metabolism, sugar transport, acid production, polysaccharide degradation, low pH growth, dental caries
- MeSH terms
- Bacterial Proteins, Biological Transport, DNA-Binding Proteins, Galactose, Glucose, Glycoside Hydrolases, Hydrogen-Ion Concentration, Polysaccharides, Repressor Proteins, Streptococcus mutans, Transcription, Genetic, Virulence, Gene Expression Regulation, Bacterial, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Electrophoretic Mobility Shift Assay
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review