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Independence from Kinetoplast DNA Maintenance and Expression Is Associated with Multidrug Resistance in Trypanosoma brucei In Vitro

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 sin...

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Detalles Bibliográficos
Autores principales: Gould, Matthew K., Schnaufer, Achim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993240/
https://www.ncbi.nlm.nih.gov/pubmed/24550326
http://dx.doi.org/10.1128/AAC.00122-14
Descripción
Sumario: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.