Induction of resistance to melarsenoxide cysteamine (Mel Cy) in Trypanosoma brucei brucei

A population of Trypanosoma brucei brucei with reduced sensitivity to melarsenoxide cysteamine (Mel Cy) was produced in immunosuppressed mice using subcurative drug treatment. Melarsenoxide cysteamine resistance was stable after cyclical transmission through Glossina morsitans centralis. In vitro, the bloodstream forms showed 15-fold higher values for the minimal inhibitory concentration as compared with the parental clone. Cross-resistance could be determined with another arsenical drug, melarsoprol (14-fold) and to two different diamidines (diminazene aceturate: 47-fold; pentamidine methanesulphonate: 34-fold), but not to suramin. When cells were transformed to procyclic forms and tested in vitro, the sensitivity of the resistant population to melarsenoxide cysteamine was only 6-fold lower than that of the parent, but comparatively high cross-resistance could be shown to other drugs (melarsoprol: 85-fold; pentamidine methanesulphonate: 17-fold; quinapyramine sulphate: 40-fold). Selection of the resistant trypanosomes from non-resistant ones was possible under pentamidine methanesulphonate pressure in cell culture.