Heinz-Given Professor of the Pre-medical Sciences and Chair, Department of Biology
Streptococcus mutans is the principal causative agent of dental caries in humans. A major research objective in the Spatafora laboratory centers on identifying genes belonging to the S. mutans SloR metalloregulome and defining their potential involvement in the caries-forming process.
Homologs of the SloR metalloregulator in other pathogenic bacteria are known to modulate gene expression upon binding DNA in the presence of a metal ion co-repressor. We propose that SloR, in response to metal ion availability in the human oral cavity, modulates metal ion transport and virulence gene expression in such as way as to promote S. mutans persistence and pathogenesis in dental plaque. The results of microarray and real-time qRT-PCR experiments revealed SloR as a pleiotropic global regulator in S. mutans. Our work is presently focused on a subset of S. mutans virulence genes that we identified are subject to both manganese and SloR control and that are preceded by a SloR recognition element (SRE) that binds the metalloregulator. One of our research goals is to explore and compare the mechanisms by which SloR regulates S. mutans gene expression and so reveal the complexities of SloR metalloregulation in this important oral pathogen. We also plan to reveal the constituency and structural organization of the SREs that precede SloR-regulated virulence genes in S. mutans, and to investigate the structure of the purified SloR protein so that the details of the SloR:SRE interaction under conditions of physiological relevance to the plaque environment can be elucidated. Taken together, we propose that manganese-dependent SloR binding to specific palindromic SREs facilitates S. mutans virulence gene expression and cariogenesis. This research is important not only because it will advance our understanding of S. mutans gene regulation but also because it will reveal a basis for designing novel therapeutic agents that can target SloR-modulated virulence gene expression and so alleviate the S. mutans-induced cariogenic process.
*Indicates a Middlebury College student
Merchant, A.* and G. Spatafora. 2014. A role for the DtxcR familhy of metalloregulators in gram positive pathogenesis. Molec. Oral Microbiol. 29:1-10.
Haswell, J.R.*, B.W. Pruitt*, L.P. Cornacchione*, C.L. Coe*, E.G. Smith* and G. Spatafora. 2013. Characterization of the functioinal domains of the SloR metalloregulatory protein in Streptococcus mutans. J. Bacteriol. 195:126-134
Smith, E.G.* and G. Spatafora. 2012. Gene Regulation in Streptococcus mutans: Complex Control in a Complex Environment. J. Dent. Res. (featured as a Critical Review in Oral Biology and Medicine) 91(2):133-141.
O’Rourke, K.P.*, J.D. Shaw*, M.W. Pesesky*, B.T. Cook*, S.M. Roberts*, J.P. Bond and G.A. Spatafora. 2010. Genome-wide characterization of the SloR metalloregulome in Streptococcus mutans. J. Bacteriol. 192:1433-43.
Levine, R.B.*, M.S. Constanza-Robinson and G. Spatafora. 2010. Neochloris oleoabundans grown on anaerobically digested dairy manure for concomitant nutrient removal and biodiesel feedstock production. Biomass and Bioenergy, 35:40-49
Dunning, D.W.*, L.W. McCall*, W.F. Powell*, W. T. Arscott*, E. M. McConocha*, S. D. Goodman, and G. Spatafora. 2008. SloR modulatioin of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary. Microbiology 154:1132-43.
Rolerson, E*, A. Swick*, L. Newlon*, C. Palmer*, Y. Pan*, B. Keeshan*, and G. Spatafora. 2006. The SloR/Dlg metalloregulator modulates Streptococcus mutans virulence gene expression. J. Bacteriol. 188:5033-5044.