Nathan Shankar, Ph.D.
Prof & Vc Chair
Phone (405) 271-6481 x47214
Fax (405) 271-7505
Office CPB 303
The increasing incidence of 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 poorly 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 identified mechanisms by which these determinants may be disseminated to other members of this species in vitro and in vivo. More recently we have begun to investigate 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.
Publications & Presentations
- 1. Zou J, Shankar N. Surface protein Esp enhances pro-inflammatory cytokine expression through NF-κB activation during enterococcal infection. Innate Immunity. 2016; 22 : 31-39
2. Zou J, Shankar N. The opportunistic pathogen Enterococcus faecalis resists phagosome acidification and autophagy to promote intracellular survival in macrophages. Cellular Microbiology. 2016; 18 : 831-843
3. Zou J, Shankar N. Roles of TLR/MyD88/MAPK/NF-κB Signaling Pathways in the Regulation of Phagocytosis and Proinflammatory Cytokine Expression in Response to E. faecalis Infection. PLoS ONE. 2015; 10 : e0136947
4. Zou J, Shankar N. Enterococcus faecalis infection activates phosphatidylinositol 3-kinase signaling to block apoptotic cell death in macrophages. Infection and Immunity. 2014; 82 : 5132-5142
5. Zou J, Baghdayan A, Payne S, Shankar N. A TIR domain protein from E. faecalis attenuates NF-κB activation induced by lipopolysaccharide and promotes intracellular survival in host cells but is not required for virulence in a murine peritonitis infection model. PLOS ONE. 2014; 9 : e:112010
- 1. Multi-modal protein and RNA visualization and quantification. Non-federal. Start Date: 2015. End Date: 2016.
2. Characterization of phagosome trafficking and autophagy in the survival of E. faecalis in macrophages. Non-federal. Start Date: 2014. End Date: 2015.
3. Structural studies of a TIR-domain protein from Enterococcus faecalis. NIH. Start Date: 2013. End Date: 2014.
Awards and Honors
- 1. OUHSC. President's Associates Presidential Professorship. Date: 2008.
2. OUHSC. Regents Award for Superior Accomplishment in Research and Creative Activity. Date: 2006.
3. OUHSC ORA. Office of Research Outstanding Research Award. Date: 2002.