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Science. 2016 Apr 15;352(6283):349-53. doi: 10.1126/science.aad9279.

Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes.

Author information

1
School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia. gim@unimelb.edu.au deang@unimelb.edu.au.
2
School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia. Eijkman Institute for Molecular Biology, JI Diponegoro no. 69, Jakarta, 10430, Indonesia. Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
3
School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia.
4
Johns Hopkins University Bloomberg School of Public Health, Department of Molecular Microbiology and Immunology, Malaria Research Institute, Baltimore, MD 21205, USA.
5
Eijkman Institute for Molecular Biology, JI Diponegoro no. 69, Jakarta, 10430, Indonesia. Department of Parasitology, Faculty of Medicine, Hasanuddin University, Jalan Perintis Kemerdekaan Km10, Makassar 90245, Indonesia.
6
Division of Medical Zoology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
7
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
8
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. School of Tropical Medicine and Global Health, Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan.
9
Eijkman Institute for Molecular Biology, JI Diponegoro no. 69, Jakarta, 10430, Indonesia.

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.

PMID:
27081071
PMCID:
PMC5149070
DOI:
10.1126/science.aad9279
[Indexed for MEDLINE]
Free PMC Article

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