Abstract
The oral pathogen Streptococcus mutans employs a variety of mechanisms to maintain a competitive advantage over many other oral bacteria which occupy the same ecological niche. Production of the bacteriocin, mutacin I, is one such mechanism. However, little is known about the regulatory mechanisms associated with mutacin I production. Previous work has demonstrated that the production of mutacin I greatly increased with cell density. In this study, we found that high cell density also triggered high level mutacin I gene transcription. However, this response was abolished upon deletion of luxS. Further analysis using real-time reverse transcription polymerase chain reaction (RT-PCR) demonstrated that in the luxS mutant transcription of both the mutacin I structural gene mutA and the mutacin I transcriptional activator mutR was impaired. Through microarray analysis, a putative transcription repressor annotated as Smu1274 in the Los Alamos National Laboratory Oral Pathogens Sequence Database was identified, which was strongly induced in the luxS mutant. Characterization of Smu1274, which we referred to as irvA, suggested that it may act as an inducible repressor to suppress mutacin I gene expression. A luxS and irvA double mutant regained the ability to produce mutacin I; whereas a constitutive irvA-producing strain was impaired in mutacin I production. These findings reveal a novel regulatory pathway for mutacin I gene expression, which may provide clues to the regulatory mechanisms of other cellular functions regulated by luxS in S. mutans.
Original language | English (US) |
---|---|
Pages (from-to) | 960-969 |
Number of pages | 10 |
Journal | Molecular Microbiology |
Volume | 57 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2005 |
Externally published | Yes |
ASJC Scopus subject areas
- Microbiology
- Molecular Biology
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In: Molecular Microbiology, Vol. 57, No. 4, 08.2005, p. 960-969.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - LuxS controls bacteriocin production in Streptococcus mutans through a novel regulatory component
AU - Merritt, Justin
AU - Kreth, Jens
AU - Shi, Wenyuan
AU - Qi, Fengxia
N1 - Funding Information: M.A.K. is funded by an NIHR Research Professorship and receives funding from the Sir Jules Thorn Award for Biomedical Research, Great Ormond Street Children’s Hospital Charity (GOSHCC) and Rosetrees Trust. M.A.K., K.E.B., L.A., D.S., A.N., N.T. and E.M. are supported by the NIHR GOSH BRC. K.M.G. received funding from Temple Street Foundation. L.A. is funded by the Swiss National Foundation. E.M. received funding from the Rosetrees Trust (CD-A53), and the Great Ormond Street Hospital Children’s Charity. A.S.J. is funded by NIHR Bioresource for Rare Diseases. S.A.I. and M.H. are supported by the NINDS Intramural program. K.P.B. is PI of the Movement disorders centre (MDC) at UCL, Institute of Neurology which has been funded by the BRC. He has grant support by EU Horizon 2020. M.E.D-H. has clinical training grant through Tourette Association of America, but the research is unrelated to KMT2B. T.L. received funding from Health Research Board, Ireland and Michael J Fox. Foundation. K.A.M. receives funding from the NIH (award number K23NS101096-01A1). N.S. receives funding from the NIH (award number NS 087997 0). D.D. was supported by KIM MUSE Biomarkers and Therapy study grant during this work. B.B.A.d.V. financially supported by grants from the Netherlands Organization for Health Research and Development (912-12-109). J.F. is funded by the Rady Children’s Institute for Genomic Medicine. F.L.R. is funded by Cambridge Biomedical Research Centre. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF-1009-003], a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute [grant number WT098051]. This research Funding Information: We thank all our patients and their families for taking part in this study. This research was supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. We also acknowledge support from the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s and St. Thomas’ National Health Service (NHS) Foundation Trust in partnership with King’s College London. The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health or Wellcome Trust. Sequencing for Patient 37 was provided by the University of Washington Center for Mendelian Genomics (UW-CMG) and was funded by the National Human Genome Research Institute and the National Heart, Lung and Blood Institute grant HG006493 to Drs Debbie Nickerson, Michael Bamshad, and Suzanne Leal. Funding Information: We thank all our patients and their families for taking part in this study. This research was supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. We also acknowledge support from the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health or Wellcome Trust. Sequencing for Patient 37 was provided by the University of Washington Center for Mendelian Genomics (UW-CMG) and was funded by the National Human Genome Research Institute and the National Heart, Lung and Blood Institute grant HG006493 to Drs Debbie Nickerson, Michael Bamshad, and Suzanne Leal. M.A.K. is funded by an NIHR Research Professorship and receives funding from the Sir Jules Thorn Award for Biomedical Research, Great Ormond Street Children's Hospital Charity (GOSHCC) and Rosetrees Trust. M.A.K., K.E.B., L.A., D.S., A.N., N.T. and E.M. are supported by the NIHR GOSH BRC. K.M.G. received funding from Temple Street Foundation. L.A. is funded by the Swiss National Foundation. E.M. received funding from the Rosetrees Trust (CD-A53), and the Great Ormond Street Hospital Children's Charity. A.S.J. is funded by NIHR Bioresource for Rare Diseases. S.A.I. and M.H. are supported by the NINDS Intramural program. K.P.B. is PI of the Movement disorders centre (MDC) at UCL, Institute of Neurology which has been funded by the BRC. He has grant support by EU Horizon 2020. M.E.D-H. has clinical training grant through Tourette Association of America, but the research is unrelated to KMT2B. T.L. received funding from Health Research Board, Ireland and Michael J Fox. Foundation. K.A.M. receives funding from the NIH (award number K23NS101096-01A1). N.S. receives funding from the NIH (award number NS 087997 0). D.D. was supported by KIM MUSE Biomarkers and Therapy study grant during this work. B.B.A.d.V. financially supported by grants from the Netherlands Organization for Health Research and Development (912-12-109). J.F. is funded by the Rady Children's Institute for Genomic Medicine. F.L.R. is funded by Cambridge Biomedical Research Centre. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF-1009-003], a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute [grant number WT098051]. This research was made possible through access to the data and findings generated by the 100 000 Genomes Project (Patient 34). The 100 000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health). The 100 000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100 000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. Research reported in this manuscript was supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director to the Undiagnosed Disease Network (UDN) and the NIH Undiagnosed Disease Program (Award numbers: U01HG007690 and U01HG007703). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: was made possible through access to the data and findings generated by the 100 000 Genomes Project (Patient 34). The 100 000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health). The 100 000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100 000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. Research reported in this manuscript was supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director to the Undiagnosed Disease Network (UDN) and the NIH Undiagnosed Disease Program (Award numbers: U01HG007690 and U01HG007703). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
PY - 2005/8
Y1 - 2005/8
N2 - The oral pathogen Streptococcus mutans employs a variety of mechanisms to maintain a competitive advantage over many other oral bacteria which occupy the same ecological niche. Production of the bacteriocin, mutacin I, is one such mechanism. However, little is known about the regulatory mechanisms associated with mutacin I production. Previous work has demonstrated that the production of mutacin I greatly increased with cell density. In this study, we found that high cell density also triggered high level mutacin I gene transcription. However, this response was abolished upon deletion of luxS. Further analysis using real-time reverse transcription polymerase chain reaction (RT-PCR) demonstrated that in the luxS mutant transcription of both the mutacin I structural gene mutA and the mutacin I transcriptional activator mutR was impaired. Through microarray analysis, a putative transcription repressor annotated as Smu1274 in the Los Alamos National Laboratory Oral Pathogens Sequence Database was identified, which was strongly induced in the luxS mutant. Characterization of Smu1274, which we referred to as irvA, suggested that it may act as an inducible repressor to suppress mutacin I gene expression. A luxS and irvA double mutant regained the ability to produce mutacin I; whereas a constitutive irvA-producing strain was impaired in mutacin I production. These findings reveal a novel regulatory pathway for mutacin I gene expression, which may provide clues to the regulatory mechanisms of other cellular functions regulated by luxS in S. mutans.
AB - The oral pathogen Streptococcus mutans employs a variety of mechanisms to maintain a competitive advantage over many other oral bacteria which occupy the same ecological niche. Production of the bacteriocin, mutacin I, is one such mechanism. However, little is known about the regulatory mechanisms associated with mutacin I production. Previous work has demonstrated that the production of mutacin I greatly increased with cell density. In this study, we found that high cell density also triggered high level mutacin I gene transcription. However, this response was abolished upon deletion of luxS. Further analysis using real-time reverse transcription polymerase chain reaction (RT-PCR) demonstrated that in the luxS mutant transcription of both the mutacin I structural gene mutA and the mutacin I transcriptional activator mutR was impaired. Through microarray analysis, a putative transcription repressor annotated as Smu1274 in the Los Alamos National Laboratory Oral Pathogens Sequence Database was identified, which was strongly induced in the luxS mutant. Characterization of Smu1274, which we referred to as irvA, suggested that it may act as an inducible repressor to suppress mutacin I gene expression. A luxS and irvA double mutant regained the ability to produce mutacin I; whereas a constitutive irvA-producing strain was impaired in mutacin I production. These findings reveal a novel regulatory pathway for mutacin I gene expression, which may provide clues to the regulatory mechanisms of other cellular functions regulated by luxS in S. mutans.
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UR - http://www.scopus.com/inward/citedby.url?scp=23744455757&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2958.2005.04733.x
DO - 10.1111/j.1365-2958.2005.04733.x
M3 - Article
C2 - 16091037
AN - SCOPUS:23744455757
SN - 0950-382X
VL - 57
SP - 960
EP - 969
JO - Molecular Microbiology
JF - Molecular Microbiology
IS - 4
ER -