"Implicit in your decision to attend graduate school is the understanding that you are ready to accept responsibility for the direction of your career. My role as mentor is to make sure you have the resources, both intellectual and physical, to allow you to succeed. If you have the drive and the interest, then I am excited to discuss ideas and my role as teacher and colleague."
Molecular analysis of group A Streptococcus pathogenesis
The Gram-positive pathogen group A Streptococcus (GAS) causes multiple human infections ranging from mild pharyngitis to severe disease including toxic shock syndrome, necrotizing fasciitis, and rheumatic fever. An overall increase in the incidence of GAS disease since the 1980s coupled with fears about the emergence of antibiotic resistance has renewed interest in the mechanisms of GAS pathogenesis and the development of new therapeutics. While the molecular basis of GAS pathogenesis is not fully understood, it is known that the pathogen produces a large number of extracellular proteins which mediate interactions with the host. In addition, genome scale analysis has revealed a complex regulatory network including 13 two-component regulatory systems and greater than 100 additional putative regulators, the majority of which remain uncharacterized. The long term goals of my laboratory are to understand the fundamental molecular mechanisms of GAS-host interactions, elucidate the regulatory networks that influence those mechanisms, and define the molecular basis of GAS reemergence.
We are currently investigating a protein which belongs to the Crp/Fnr family of transcriptional regulators named Srv (Streptococcal regulator of virulence). Inactivation of srv results in a dramatic reduction in GAS virulence, and a recent microarray analysis indicates Srv influences the expression of numerous GAS genes. Studies are underway to determine which genes are directly affected by Srv and how srv expression changes in different host environments.
We are also studying a GAS surface protein (designated Slr for streptococcal leucine-rich) containing 10 and one-half sequential units of a 22 amino acid C-terminal leucine-rich repeat (LRR). In general, the LRR motif forms a structural unit consisting of a ß strand and an α helix, which occurs from 1-30 times in tandem arrays. The resulting horseshoe-shaped molecule provides a versatile scaffold for protein-protein interactions. A diverse array of functions have been described for LRR proteins including ribonuclease inhibition, GTPase activation, and virulence. Initial evidence from our investigation indicates that Slr contributes to the ability of GAS to avoid phagocytosis by human polymorphonuclear cells, thereby allowing the pathogen to disseminate.
Selected Publications
Reid, S. D., Hong, W., Dew, K. E., Winn, D. R., Pang, B., Watt, J. M., Glover, D. T., Hollingshead, S. K., Swords, W. E. 2008. Streptococcus pneumoniae forms surface attached biofilm communities within the middle-ear chamber of experimentally infected chinchillas. J. Infect. Dis. In Press.
Doern, C. D., Holder, R. C. and S. D. Reid. 2008. Point Mutations Within the Streptococcal Regulator of Virulence (Srv) Alter Protein/DNA Interactions and Srv function. Microbiology. In Press.
Reid, S. D., Chaussee, M. S., Doern, C. D., Chaussee, M. A., Montgomery, A. G., Sturdevant, D. E., and J. M. Musser. 2006. Inactivation of the group A Streptococcus regulator srv results in global reduction of transcript levels, and changes in extracellular protein production. FEMS Immuno. Med. Micro. 48:283-292
Reid, S. D., A. G. Lee, and J. M. Musser. 2004. Identification of srv, a PrfA-like regulator of group A Streptococcus that influences virulence. Infect. Immun. 72:1799-1803.
Reid, S. D., A. G. Lee, J. M. Voyich, F. R. DeLeo, B. Lei, R. M. Ireland, N. M. Green, M. Liu, S. Lukomski, and J. M. Musser. 2003. Characterization of an extracellular virulence factor made by Group A Streptococcus with homology to the Listeria monocytogenes internalin family of proteins. Infect. Immun. 71:7043-7052
Reid, S. D., N. M. Green, J. K. Buss, B. Lei, and J. M. Musser. 2001. Multilocus analysis of extracellular putative virulence proteins made by group A Streptococcus: population genetics, human serologic response, and gene transcription. Proc. Natl. Acad. Sci. 98:7552-7557.
Reid, S. D., N. P. Hoe, L. M. Smoot, and J. M. Musser. 2001. Group A Streptococcus: allelic variation, population genetics, and host-pathogen interactions. J. Clin. Invest. 107:393-399
PubMed link to Reid SD