title: Independence from Kinetoplast DNA maintenance and expression is associated with multidrug resistance in Trypanosoma brucei in vitro.
abstract: It is well known that several antitrypanosomatid 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 the dependence of laboratory strains of the sleeping sickness parasite Trypanosoma brucei on a functional kinetoplast result in significant resistance to the diamidine and phenanthridine drug classes.
authors.affiliation: Centre for Immunity, Infection & Evolution, Institute of Immunology & Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Gould
authors.forename: Achim
authors.initials: A
authors.lastname: Schnaufer
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology; D018105:DNA, Kinetoplast / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000981:Antiprotozoal Agents; D018105:DNA, Kinetoplast