Vice Chair - Pharm Sciences
nathan-shankar@ou.edu
The continuing battle against emerging antibiotic resistance has brought a new sense of urgency to the discovery and development of antibacterial drugs. Effectively conquering antibiotic resistance will require expanding the available targets. One approach to this problem is to identify new targets by panning the genomes of antibiotic resistant bacteria. Enterococci, Gram-positive bacteria normally growing as commensal organisms of the gut, have emerged as a leading cause of nosocomial (hospital-acquired) infections and are frequently resistant to multiple antibiotics. Although the ability of Enterococcus faecalis to cause serious disease is well recognized, much remains to be learnt about enterococcal virulence factors that contribute to pathogenesis. For instance, factors that may influence the ability of enterococci to colonize host tissues, translocate across epithelial barriers or survive in grossly different host environments are not fully understood. Our laboratory is interested in the identification of potential virulence determinants in E. faecalis that may play a role in enterococcal pathogenesis. We have identified, surface anchored enterococcal proteins that mediate biofilm formation, the first E. faecalis pathogenicity island encoding a large number of potential virulence determinants, and mechanisms by which these determinants may be disseminated to other members of this species in vitro and in vivo. More recently we have investigated some of the mechanisms by which enterococci may disrupt host immune defense systems to promote bacterial survival and cause systemic disease. We are currently actively studying an enterococcal protein that interferes with host Toll-like receptor (TLR) signaling, employing a variety of biochemical, immunological and structural biology approaches along with murine models of infection. More recently, we have become interested in developing and using machine learning and artificial intelligence approaches to drug discovery and drug repurposing.