Alternative treatment options for cryptococcal meningitis: the search for amphotericin B synergists

Cryptococcal meningitis is a fatal disease that is most commonly found in immunosuppressed individuals, particularly HIV patients. Initial treatment is with a combination of Amphotericin B (AmB) and 5-Flucytosine. 5-flucytosine is expensive and unavailable in many of the countries where the burden of disease is highest. Developing a new combination therapy that is less expensive and more accessible would benefit a large population of people suffering from these infections. I performed a high-throughput screen to identify drugs that act synergistically with AmB and validated putative synergists using the checkerboard method. Oseltamivir phosphate, dipyridamole, chlorpromazine, and morin hydrate were validated as AmB synergists. Gene knockout strains of C. neoformans were then used to inform hypotheses about the mechanisms by which oseltamivir phosphate inhibits Cryptococcus neoformans growth