Polyamine depletion and growth inhibition of Cryptococcus neoformans by alpha-difluoromethylornithine and cyclohexylamine.
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 Cryptococcus neoformans was examined. Treatment of C. neoformans with either DFMO or cyclohexylamine resulted in depletion of cellular polyamines and inhibition of growth. Cryptococcus neoformans was shown to lack detectable spermine and to require high concentrations of spermidine, but not putrescine, for growth. The growth inhibition by DFMO and cyclohexylamine was reversed by exogenous polyamines. These findings document the ability of cyclohexylamine and DFMO to inhibit polyamine synthesis and growth in clinically important isolates of C. neoformans.
Pfaller
M A
MA
Veterans Administration Medical Center, Iowa City, IA.
Riley
J
J
Gerarden
T
T
D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D003514:Cyclohexylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology*; D006801:Humans; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000096:biosynthesis; D013095:Spermidine / Q000096:biosynthesis; D013096:Spermine / Q000096:biosynthesis
D003514:Cyclohexylamines; D011073:Polyamines; D013096:Spermine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine