Journal article
Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes
CD Goodman, JE Siregar, V Mollard, J Vega-Rodríguez, D Syafruddin, H Matsuoka, M Matsuzaki, T Toyama, A Sturm, A Cozijnsen, M Jacobs-Lorena, K Kita, S Marzuki, GI McFadden
Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2016
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 outcro..
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Awarded by National Institutes of Health
Funding Acknowledgements
This work was supported by grants from the National Health and Medical Research Council (Australia); the Australian Research Council; the Indonesian Ministry of Research, Technology, and Higher Education; the U.S. National Institutes of Health (grants AI031478 and RR00052); the Japanese Society for Promotion of Science (JSPS) KAKENHI (grant 23117004 to M. M. and 26253025 to K. K.); and Japanese Science and Technology Agency/Japan International Cooperation Agency Science and Technology Research Partnership for Sustainable Development (SATREPS; no. 10000284 to K. K.). We acknowledge support of the Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry (BRAIN) and the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry. J.E.S. was a JSPS Ph.D. fellow (RONPAKU program) and an Endeavor Fellow from Scope Global, Australia. A.S. is affiliated with TropIQ Health Sciences (http://tropiq.nl). We thank the Johns Hopkins Malaria Research Institute mosquito and parasite core facilities for help with mosquito rearing and P. falciparum cultures, S. Narulitha of the Eijkman Institute for Molecular Biology for the novel P. berghei PbM133I atovaquone resistance mutant, and Walter Reed Army Institute of Research for the P. falciparum NF54e parasites. Data are archived at figshare (https://figshare.com) under doi 10.4225/49/56DE29B278684.