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Journal of Antimicrobial Chemotherapy (2001) 47, 491-494
© 2001 The British Society for Antimicrobial Chemotherapy

Brief report

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

Elias K. Manavathua,*, Jonathan R. Dimmockb, Sarvesh C. Vashishthab and P. H. Chandrasekara

a Division of Infectious Diseases, Department of Internal Medicine, 427 Lande Building, Wayne State University, 550 E. Canfield, Detroit, MI 48201, USA; b College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

We investigated the in vitro susceptibility of clinical isolates of Cryptococcus neoformans to the novel conjugated styryl ketone NC1175 by broth microdilution. The MIC90 and the MFC of NC1175 for C. neoformans were 1 and 2 mg/L, respectively. NC1175 at low concentrations (1–4 mg/L) completely inhibited 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. neoformans and its possible cellular target(s) include the H+-ATPase.

* Corresponding author. Tel: +1-313-577-1931; Fax: +1-313-993-0302; E-mail: aa1388{at}wayne.edu


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