We are pleased to announce that Daria Van Tyne, PhD, has been awarded funding in the amount of $159,000 for a two-year grant by the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) entitled “Carbonic anhydrase inhibition as a target for antibiotic synergy in enterococci.” This proposal was submitted in response to the funding opportunity entitled “NIH Small Research Project Grant (Parent R03 Clinical Trial Not Allowed)” under funding opportunity announcement PA-20-200.
Enterococcus faecalis is a hospital-associated opportunistic pathogen that causes infections with high morbidity and mortality. An increasing occurrence of multidrug-resistant enterococci has driven the need for alternative treatment strategies to combat these pathogens.
Previously, the Van Tyne Laboratory isolated and characterized an unusual gentamicin hypersusceptible E. faecalis strain that was cultured from a patient with infective endocarditis. Separately, they also observed that the carbonic anhydrase inhibitor acetazolamide and gentamicin together displayed synergistic activity at inhibiting the growth of wild type E. faecalis strains. These findings led them to hypothesize that disruption of carbonic anhydrases can sensitize E. faecalis to killing with aminoglycosides. This funded proposal will facilitate elucidation of the mechanistic basis of this synergy, and will examine whether disruption of the E. faecalis alpha-carbonic anhydrase causes increased gentamicin uptake via proton motive force-dependent transport and/or increased membrane permeability. Additionally, they will investigate differential synergy between aminoglycosides and chemically diverse carbonic anhydrase inhibitors against isogenic E. faecalis strains expressing different carbonic anhydrase genotypes. This project will increase our understanding of E. faecalis biology, while also providing important pilot data toward the development of a promising new combination therapy for patients with enterococcal infections.
Please join us in congratulating Daria!