The incidence of endophthalmitis, a potentially blinding infection of the interior of the eye is becoming an ever more important public health problem, since intraocular procedures have experienced exponential growth in recent years. The molecular pathogenesis of endophthalmitis (and many other bacterial infections) is poorly understood, and potential therapeutic avenues therefore remain unexplored. S. aureus is the most important cause of severe endophthalmitis (and many other sever infections), with less than half of patients regaining vision better than 20/200, the cutoff for legal blindness. S. aureus will be the focus of the proposed research. The overarching goal of this project is to characterize the organisms causing severe ocular S. aureus infections, and use endophthalmitis as a model of disease that affords an unparalleled view of the mechanisms involved in the molecular pathogenesis of bacterial infection. The specific goals of this project are to (i) collect and characterize bacterial isolates from ocular infections in a collaborative fashion both locally, nationally and internationally, and characterize them on the molecular level, (ii) analyze the host-pathogen interactions that lead to an untoward outcome in S. aureus endophthalmitis by employing genetically modified bacterial strains and knockout host organisms in animal models developed by the principal investigator, and (iii) therapeutically modulate bacterial gene expression and the host response based on the knowledge gleaned from (i) and (ii) to improve visual outcome of patients with endophthalmitis, or other severe staphylococcal infections. The principal investigator has an established network of collaborators both on the NYU Campus (R.Novick Ph.D., B. Shopsin M.D.) and outside of NYU both in New York (R. Rosen M.D., NYEE; S.C. Chang M.D., Columbia University) and outside (M.S. Gilmore Ph.D., Harvard University; H. Flynn M.D., Bascom Palmer Eye Institute; H. Mi?o de Kaspar Ph.D., Stanford University and Munich University, Germany) that allows for collaborative collection of bacterial strains and to monitor emerging etiologic trends nationally and internationally.
