Atovaquone Tolerance in Plasmodium falciparum Parasites Selected for High-Level Resistance to a Dihydroorotate Dehydrogenase Inhibitor | Zendy

Jennifer L. Güler | Zendy; John White | Zendy; Margaret A. Phillips | Zendy; Pradipsinh K. Rathod | Zendy

Open Access

Atovaquone Tolerance in Plasmodium falciparum Parasites Selected for High-Level Resistance to a Dihydroorotate Dehydrogenase Inhibitor

Author(s) -

Jennifer L. Güler,

John White,

Margaret A. Phillips,

Pradipsinh K. Rathod

Publication year - 2014

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.02347-14

Subject(s) - dihydroorotate dehydrogenase , atovaquone , malaria , plasmodium falciparum , biology , pyrimidine metabolism , drug resistance , pharmacology , microbiology and biotechnology , immunology , genetics , pyrimidine , biochemistry , enzyme , purine

Atovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level resistance to an inhibitor of dihydroorotate dehydrogenase demonstrate unexpected atovaquone tolerance. Fortunately, the tolerance is diminished with proguanil, the second partner in Malarone. It is important to understand such "genetic cross talk" between respiration and pyrimidine biosynthesis since many antimalarial drug development programs target these two seemingly independent pathways.

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