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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.

SUBMITTER: Gould MK

PROVIDER: S-EPMC3993240 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Independence from Kinetoplast DNA maintenance and expression is associated with multidrug resistance in Trypanosoma brucei in vitro.

Gould Matthew K MK Schnaufer Achim A

Antimicrobial agents and chemotherapy 20140218 5

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 p ...[more]

PMID: 24550326

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