Reid Laboratory

Sean Reid

Assistant Professor
B.S., Bucknell University, 1994
Ph.D., Pennsylvania State University, 2000

e-mail: sreid@wakehealth.edu
phone: (336) 716-9529 

"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.

Rather than exploit a singular niche, GAS has evolved to colonize and disseminate within several physiologically distinct anatomical sites of the human host. One means by which this can be achieved is though the formation of a biofilm, a 3-dimensional bacterial community encased in a protective matrix. Such versatility requires the ability to coordinately regulate the expression and production of numerous factors in rapid response to host and environmental signals in order to facilitate attachment, biofilm formation, and eventual dispersal (dissemination). We have recently discovered that GAS can modulate biofilm dispersal through the tight regulation of the streptococcal cysteine protease (SpeB) by the streptococcal regulator of virulence (Srv). Study of this mechanism in different serotypes of GAS suggests that it is broadly conserved. Interestingly, in the study of two disparate models of GAS disease, GAS was found to naturally form biofilms, but biofilms were not required for infection and were not associated with impaired clearance of the organism. Rather, a strain locked-on for biofilm dispersal was associated with more severe disease in both models. Taken together, this data suggests a model by which Srv regulated control of biofilm dispersal through the action of SpeB may provide an efficient means for dissemination of the organism to susceptible hosts. Unregulated dispersal of the GAS biofilm however, leads to increased virulence and severe disease.