Independence from kinetoplast DNA maintenance and expression is associated with multi-drug resistance in Trypanosoma brucei in vitro

It is well known that several anti-trypanosomatid drugs accumulate in the parasite's mitochondrion, where they often bind to the organellar DNA, the kinetoplast. To what extent this property relates to the mode of action of these compounds has remained largely unquantified. Here we show that single point mutations that remove dependence of laboratory strains of the sleeping sickness parasite Trypanosoma brucei on a functional kinetoplast result in significant resistance to diamidine and phenanthridine class drugs.