||University of Toronto
My research focus is to use oral microbiomics to examine bacterial shifts during conditions that compromise oral and systemic health (for example, hyposalivation, diabetes, obesity, etc.). My research aims to answer two questions: 1) How do bacterial communities in the human body shift during health and disease states? 2) How can knowledge of health- and disease-associated microbiota be used for our benefit with translational applications? Using next-generation DNA sequencing, bioinformatics, machine learning, and molecular microbiological methods, my goal is to discover oral bacterial biomarkers to facilitate the development of novel aids for infection risk prediction, diagnostics, prognostics and therapeutics.
Another focus of my research is to break new ground in oral medicine and develop a next-generation artificial mouth model for in vitro surveillance and manipulation of oral plaque suspensions. My vision is to use this model for novel drug testing and to examine the possibility to restore the function of a dysbiotic community with health-associated beneficial microbiota using defined probiotics or whole-plaque bacterial therapy (i.e. plaque transplantation).
- M.W. Hall, N. Wellapulli, K. Singh, D.G.Cvitkovitch, D. K. Lam, M. Glogauer, R. Beiko, D.B. Senadheera. 2020. Bacterial succession in the oral microbiome during the onset and resolution of experimentally-induced gingivitis. Nature, Biofilms and Microbiomes, Submitted, May 2020.
- M. Oveisi, H. Shifman, N. Fine, C. Sun, N. Glogauer, D. Senadheera, M. Glogauer. 2018. Novel Assay to characterize neutrophil responses to oral biofilms. Infection and Immunity, PMID: 30455195 (E-pub ahead of print)
- M.W. Hall, N. Singh, K. F Ng, M. B. Goldberg, D. K. Lam, H.C. Tenenbaum, J.D. Neufeld, R. Beiko, D.B. Senadheera. 2017. Inter-personal diversity and temporal dynamics of dental, tongue, and salivary microbiota in the healthy oral cavity. Nature, Biofilms and Microbiomes, 3(1):2.
- I.B. Wenderska, A. Latos, B. Pruitt, S. Palmer, G. Spatafora, D.B. Senadheera*, and D.G. Cvitkovitch*(2017). Transcriptional profiling of the oral pathogen Streptococcus mutans in response to Competence Signaling Peptide XIP. mSystems, 2(1), e00102-16. *co-senior corresponding author.
- V. Galimanas, M.W. Hall, N. Singh, M.D.J. Lynch, M. Goldberg, H. Tenenbaum, D.G. Cvitkovitch, J.D. Neufeld, D.B. Senadheera. 2014. Bacterial community composition of chronic periodontitis and novel oral sampling sites for detecting disease indicators. Microbiome. 2(32). PMC4164120.
- R.N. Besingi, I.B. Wenderska, D.B. Senadheera, D.G. Cvitkovitch, J.R. Long, Z.T. Wen, and L.J. Brady. 2017. Functional amyloids in Streptococcus mutans, their use as targets of biofilm inhibition and initial characterization of SMU_63c. Microbiology (E-pub ahead of print).
- G. Binepal, I.B. Wenderska, P. Crowley, R.N. Besingi, D.B. Senadheera, J.L. Brady, D.G. Cvitkovitch. 2017. K+ modulates genetic competence and the stress regulon of Streptococcus mutans. Microbiology (in press).
- G. Binepal, K. Gill, P. Crowley, D.B. Senadheera, and D.G. Cvitkovitch. 2016. The Trk2 potassium transport system in Streptococcus mutans and its role in potassium homeostasis, biofilm formation and stress tolerance. Journal of 198(7):1087-100. PMC4800877.
- K. Singh, D.B. Senadheera, C. Lévesque, D.G. Cvitkovitch. 2015. The copYAZ operon functions in copper efflux, biofilm formation, genetic transformation and stress tolerance in Streptococcus mutans. Journal of Bacteriology. 197(15): 2545-57. PMC4518833.
- J.S. Downey, L. Mashburn-Warren, E. A. Ayala, D.B. Senadheera, W.K. Hendrickson, L.W. McCall, J.G. Sweet, D.G. Cvitkovitch, G.A. Spatafora, S.D. Goodman. 2014. In vitro manganese-dependent cross-talk between Streptococcus mutans VicK and GcrR: Implications for overlapping stress response pathways. PLoS One. 9(12): e115975. PMC4275253.
- M.A. Serbanescu, M. Cordova, K. Krastel, R. Flick, N. Beloglazova, A. Latos, A. F. Yakunin, D.B. Senadheera and D.G. Cvitkovitch. 2014. Role of the Streptococcus mutans CRISPR/Cas systems in immunity and cell physiology. Journal of Bacteriology. 197(4): 749–761. PMC4334182.
- E. Ayala, J.S. Downey, L. Mashburn-Warren, D.B. Senadheera, D.G. Cvitkovitch, S.D. Goodman. 2014. A biochemical characterization of the DNA binding activity of the responseregulator VicR from Streptococcus mutans. PLoS One. 9(9): e108027. PMCID: PMC4168254.
- Vergauwen, K. Verstraete, D.B. Senadheera, A. Dansercoersp;D.G. ;E. ;S.N. Savvides. 2013. Molecular and structural basis of glutathione import in Gram-positive bacteria via GshT and the cystine ABC importer TcyBC of Streptococcus mutans. Molecular Microbiology. 89(2):288-303. PMID: 23701283.
- Å. Nylander, G. Svensäter, D.B. Senadheera, D.G. Cvitkovitch, J.R. Davies, K. Persson. Structural and functional analysis of the N-terminal domain of the Streptococcus gordonii adhesion. 2013. PLoS One. 17:8(5). PMC3656908.
- Q. Zhang, S.D. Wang, X.D. Zhou, L. Cheng, Y.Q. Li, D.B. Senadheera, D.G. Cvitkovitch. Functional analysis of VicK kinase activity in Streptococcus mutans (Article in Chinese). 2013. Journal of Sichuan University, Medical Sciences edition. PMID: 24490500.
- C. Wang, J. Sang, J. Wang, M. Su, J.S. Downey, Q. Wu, S. Wang, Y. Cai, X. Xu, J. Wu, D.B. Senadheera, D.G. Cvitkovitch, L. Chen, S.D. Goodman, A. Han. 2012. Mechanistic Insights Revealed by the Crystal Structure of a Histidine Kinase with Signal Transducer and Sensor Domains. PloS Biology. 11(2). PMID: 23468592
- D.C. Hung, J.S. Downey, E.A. Ayala, J. Kreth, R. Mair, D.B. Senadheera, F. Qi, D.G. Cvitkovitch, W. Shi, S.D. Goodman. 2011. Characterization of DNA binding sites of the ComE response regulator from Streptococcus mutans. Journal of Bacteriology. 193:3642-52. PMC3306399.
- J.C. Stearns, M.D.J. Lynch, D.B. Senadheera, H.C. Tenenbaum, M.B. Goldberg, D.G. Cvitkovitch, K. Croitoru, G. Moreno-Hagelsieb, J.D. Neufeld. 2011. Bacterial biogeography of the human digestive tract. Nature, Scientific Reports. 1:170. PMC3240969.
- J. Kim, D.B. Senadheera, C.M. Lévesque, D.G. Cvitkovitch. 2011. TcyR regulates l-cystine uptake via the TcyABC transporter in Streptococcus mutans. FEMS Microbiology Letters. 328(2):114-21. PMC3288405.
- K. Krastel, D. Senadheera, R Mair, J.S. Downey, S.D. Goodman, D.G. Cvitkovitch. 2009. Characterization of a Glutamate Transporter Operon, glnQHMP, in Streptococcus mutans and its role in Acid Tolerance. Journal of Bacteriology. 192(4):984-993. PMC2812961.
- P. Suntharalingam, D. Senadheera, R.W. Mair, C. M. Levesque, and D.G. Cvitkovitch. 2009. The LiaFSR system regulates the cell envelope stress response in Streptococcus mutans. Journal of Bacteriology. 191:2973-84. PMC2681809.
- I. Wenderska, N. Lukenda, M. Cordova, N. Magarvey, D.G. Cvitkovitch, D.B. Senadheera. 2012. A novel function for the competence inducting peptide, XIP, as a cell death effector of Streptococcous mutans. FEMS Microbiology Letters. 336(2):104-112. PMID: 22900705.
- D.B. Senadheera, M. Cordova, E. A. Ayala, L.E. Chávez de Paz, K. Singh, J. S. Downey, G. Svensäter, S.D. Goodman, D.G. Cvitkovitch. 2012. Regulation of bacteriocin production and cell death by the VicRK signaling system in Streptococcus mutans. Journal of Bacteriology. 194(6):1307-16. PMID: 22228735
- R.W. Mair, D.B. Senadheera*, D.G. Cvitkovitch. 2012. CinA is regulated via ComX to modulate genetic transformation and cell viability in Streptococcus mutans. FEMS Microbiology Letters. 331(1):44-52. *Corresponding author. PMC3343223.
- D. Senadheera, K. Krastel, R. Mair, A. Persadmehr, J. Abranches, R. Burne, D. G. Cvitkovitch. 2009. Inactivation of VicK affects acid production and acid survival of Streptococcus mutans. Journal of Bacteriology. 191(20):6415-24. PMC2753040.
- D. Senadheera, A.W.C. Lee, D.C. I. Hung, G.A. Spatafora and D.G. Cvitkovitch. 2007. The Streptococcus mutans vicX gene product modulates gtfB/C expression, biofilm formation, genetic competence and oxidative stress tolerance. Journal of Bacteriology. 189(4):1451-58. PMC1797355.
- D. Senadheera, B. Guggenheim, G.A. Spatafora, Y.C. Huang, J. Choi, D.C. I. Hung, J.S. Treglown, S.D. Goodman, R.P. Ellen and D.G. Cvitkovitch. 2005. A VicR/K signal transduction system in Streptococcus mutans affects gtfBCD, gbpB and ftf expression, biofilm formation and genetic competence development. Journal of Bacteriology. 187(12):4064-76.PMC1151735.
- K. Singh, D.B. Senadheera, D. G. Cvitkovitch. 2014. An intimate link: two-component signal transduction systems and metal transport systems in bacteria. Future Microbiology. 9(11): 1283-1293.
- D. Senadheera and D.G. Cvitkovitch. 2008. Quorum sensing and biofilm formation by Streptococcus mutans. Book chapter in Bacterial Signal Transduction: Networks and Drug Targets. Edited by Ryutaro Utsumi for the Advances in Experimental Medicine and Biology series, volume 631, published by Landes Bioscience, New York, U.S.A.
- D. Senadheera, C.M. Lévesque and D.G. Cvitkovitch. 2006. Cell density dependent regulation of streptococcal competence. Book chapter in Bacterial Cell-to-Cell Communication: Role in Virulence and Pathogenesis. Edited by D. R. Demuth and R.J. Lamont for the Volume 7 in the Advances in Molecular and Cellular Microbiology series published by the American Society of Microbiology. Cambridge University Press, U.K.
- D. Senadheera, C.M. Lévesque and D.G. Cvitkovitch. 2005. Signal peptide pheromones in oral streptococcal biofilms. Review article in Australia Microbiology Journal, 26 (3): 124-6.
- D. Senadheera, F.Qi and D.G. Cvitkovitch. 2008. Quorum sensing in streptococci. Book chapter in Control of Biofilm Infections by Signal Manipulation, volume 2, edited by Naomi Balaban. Springer series on biofilms, Berlin-Heildelberg.