Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes

Drug resistance compromises control of malaria. Here, we show that resistance to a commonly used antimalarial medication, atovaquone, is apparently unable to spread. Atovaquone pressure selects parasites with mutations in cytochrome b, a respiratory protein with low but essential activity in the mam...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2016-04, Vol.352 (6283), p.349-353
Main Authors: Goodman, Christopher D., Siregar, Josephine E., Mollard, Vanessa, Vega-Rodríguez, Joel, Syafruddin, Din, Matsuoka, Hiroyuki, Matsuzaki, Motomichi, Toyama, Tomoko, Sturm, Angelika, Cozijnsen, Anton, Jacobs-Lorena, Marcelo, Kita, Kiyoshi, Marzuki, Sangkot, McFadden, Geoffrey I.
Format: Article
Language:English
Subjects:
Animals
Anopheles - parasitology
Antimalarials - pharmacology
Antimalarials - therapeutic use
Antiretroviral drugs
Atovaquone - pharmacology
Atovaquone - therapeutic use
Cell Line
Cytochromes b - genetics
Disease transmission
Drug Resistance - genetics
Genes, Mitochondrial - genetics
Humans
Life Cycle Stages - drug effects
Life Cycle Stages - genetics
Malaria
Malaria - drug therapy
Malaria - parasitology
Malaria - transmission
Male
Mice
Mitochondria - genetics
Mosquitoes
Mutation
Parasites
Plasmodium berghei - drug effects
Plasmodium berghei - genetics
Plasmodium berghei - growth & development
Selection, Genetic
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Summary:Drug resistance compromises control of malaria. Here, we show that resistance to a commonly used antimalarial medication, atovaquone, is apparently unable to spread. Atovaquone pressure selects parasites with mutations in cytochrome b, a respiratory protein with low but essential activity in the mammalian blood phase of the parasite life cycle. Resistance mutations rescue parasites from the drug but later prove lethal in the mosquito phase, where parasites require full respiration. Unable to respire efficiently, resistant parasites fail to complete mosquito development, arresting their life cycle. Because cytochrome b is encoded by the maternally inherited parasite mitochondrion, even outcrossing with wild-type strains cannot facilitate spread of resistance. Lack of transmission suggests that resistance will be unable to spread in the field, greatly enhancing the utility of atovaquone in malaria control.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aad9279