2015
DOI: 10.1016/j.parint.2014.09.011
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Direct evidence for the atovaquone action on the Plasmodium cytochrome bc 1 complex

Abstract: Atovaquone, a coenzyme Q analogue has been indicated to specifically target the cytochrome bc1 complex of the mitochondrial respiratory chain in the malarial parasite and other protozoan. Various mutations in the quinone binding site of the cytochrome b gene of Plasmodium spp. such as M133I, L144S, L271V, K272R, Y268C, Y268S, Y268N, and V284F are suggesting to associate with resistance to atovaquone. There is no direct evidence of relation between the mutations and resistance to atovaquone in Plasmodium parasi… Show more

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Cited by 75 publications
(64 citation statements)
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“…fected by mutations in the target proteins that confer resistance to atovaquone or DSM265 (51,52). Identification of a specific inhibitor of isoprenoid precursor biosynthesis.…”
Section: Resultsmentioning
confidence: 99%
“…fected by mutations in the target proteins that confer resistance to atovaquone or DSM265 (51,52). Identification of a specific inhibitor of isoprenoid precursor biosynthesis.…”
Section: Resultsmentioning
confidence: 99%
“…Various single nucleotide polymorphisms (SNPs) in the quinine binding site of the Plasmodium species cytochrome b (cytb) gene have been implicated in conferring resistance to ATQ (6). While M133I and L271V have been implicated in murine malarial models (7,8), and L144S, K272R, and V284F have been demonstrated in cultures exposed to high concentrations of ATQ (9), SNPs in position 268 (Y268C, Y268S, and Y268N) have been associated with clinical failure (10). ATQ resistance also appears to be associated with the delayed recrudescence of resistant parasites Ն3 weeks after initial clearance of parasitemia by ATQ-PG therapy (11).…”
mentioning
confidence: 99%
“…3, showing the transmembrane arrangement of the apoprotein, while a similar repeated incomplete treatment (RIcT) but with a higher, therapeutic dose of the drug led to resistance mutations mostly in the Qo2 domain. The sites correspond to the degree of resistance conferred by the mutations; the level of atovaquone resistance associated with mutations in the Qo1 domain has been shown to be at least 20 times lower than that associated with mutations in the Qo2 domain in P. berghei (8). Atovaquone resistance mutations in both Qo1 (M133I) and Qo2 (Y268S) have been reported for the human malaria parasite Plasmodium falciparum.…”
Section: Discussionmentioning
confidence: 99%
“…The relationship between mutations in the Qo1 and Qo2 domains of the cytochrome b protein and the degree of resistance to atovaquone has been reported (4,8). A structural interaction between atovaquone and the cytochrome b protein has also been proposed (9).…”
Section: Dose-dependent Selection Of Atovaquone Resistance Antimicrobmentioning
confidence: 99%
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