Polyamine depletion and growth inhibition inCandida albicansandCandida tropicalisby α-difluoromethylornithine and cyclohexylamine

Abstract

The ability of two known inhibitors of polyamine synthesis, alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and cyclohexylamine, an inhibitor of spermidine synthase, to inhibit the in vitro growth and polyamine synthesis of clinical isolates of Candida tropicalis and Candida albicans was examined. Treatment of C. tropicalis and C. albicans with either DFMO or cyclohexylamine resulted in depletion of cellular polyamines and inhibition of growth. The growth inhibition produced by each of these compounds was completely reversed by exogenous polyamines. Depletion of polyamines by low concentrations of DFMO significantly enhanced the growth inhibitory activity of cyclohexylamine versus C. albicans. DFMO inhibited ODC activity in both C. albicans and C. tropicalis. These findings document the ability of cyclohexylamine and DFMO to inhibit polyamine synthesis and growth in clinically important species of Candida.