Inhibition of H+-ATPase-mediated proton pumping in Cryptococcus neoformansby a novel conjugated styryl ketone

We investigated the in vitro susceptibility of clinical isolates of Cryptoc occus neoformans to the novel conjugated styryl ketone NC1175 by broth micr odilution. The MIC90 and the MFC of NC1175 for C. neoformans were 1 and 2 m g/L, respectively. NC1175 at low concentrations (1-4 mg/L) completely inhib ited the glucose-induced acidification of the external medium caused by the extrusion of intracellular protons mediated by the plasma membrane located H+-ATPase. These data suggest that NC1175 is a fungicidal agent for C. neo formans and its possible cellular target(s) include the H+-ATPase.