Apr 20th, 1:00 PM - 4:00 PM
Evaluation of MTA/SAH Nucleosidase Inhibitors as Potential Antibiotics for Lyme Disease
Dr. Ken Cornell
Drug development against bacterial pathogens lags behind the emergence of antibiotic resistance, creating an urgent need for the identification of physiological and metabolic target unique to pathogens. One such class of molecules is the MTA/ SAH nucleosidases involved in purine and methionine salvage, polyamine synthesis and production of quorum sensing autoinducers. Nucleosidase inhibition should cause an accumulation of intracellular MTA and SAH that can selectively kill microbes or significantly diminish their growth within a host. Lyme disease causing Borrelia burgdorferi is a prevalent pathogen that produces three MTA/SAH nucleosidases; Pfs, Bgp and MtnN. We have determined the potency of four MTA/ SAH nucleosidase inhibitors on Pfs and Bgp activity. We further employed structure-based modeling to evaluate the molecular basis of the functional activities of these inhibitors on Bgp and Pfs nucleosidases.