Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes

Christopher D. Goodman, Josephine E. Siregar, Vanessa Mollard, Joel Vega-Rodríguez, Din Syafruddin, Hiroyuki Matsuoka, Motomichi Matsuzaki, Tomoko Toyama, Angelika Sturm, Anton Cozijnsen, Marcelo Jacobs-Lorena, Kiyoshi Kita, Sangkot Marzuki, Geoffrey I. McFadden

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)349-353
Number of pages5
JournalScience
Volume352
Issue number6283
DOIs
StatePublished - Apr 15 2016

ASJC Scopus subject areas

  • General
  • Medicine(all)

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    Goodman, C. D., Siregar, J. E., Mollard, V., Vega-Rodríguez, J., Syafruddin, D., Matsuoka, H., Matsuzaki, M., Toyama, T., Sturm, A., Cozijnsen, A., Jacobs-Lorena, M., Kita, K., Marzuki, S., & McFadden, G. I. (2016). Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes. Science, 352(6283), 349-353. https://doi.org/10.1126/science.aad9279