Spermidine is essential for normal proliferation of trypanosomatid protozoa

Trypanosomatid parasites containing a metabolically unstable ornithine deca rboxylase (ODC) are naturally resistant to high levels of oc-difluoromethyl ornithine (DFMO) because this ODC inhibitor, though causing a drastic reduc tion of intracellular putrescine, elicits only a moderate decrease of the s permidine endogenous pool. In this study we have used a combination of DFMO with cyclohexylamine (CHA; bis-cyclohexylammonium sulfate), an inhibitor o f spermidine synthase, to reach a more complete depletion of spermidine. Un der these conditions we have observed the arrest of proliferation not only in trypanosomatids with stable ODC but also in parasites with an enzyme of high turnover rate. In all cases the reinitiation of proliferation occurred only after the addition of exogenous spermidine, and neither putrescine no r spermine were able to induce the same effect. (C) 2001 Federation of Euro pean Biochemical Societies. Published by Elsevier Science B.V. All rights r eserved.