TY - JOUR
T1 - Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes
AU - Goodman, Christopher D.
AU - Siregar, Josephine E.
AU - Mollard, Vanessa
AU - Vega-Rodríguez, Joel
AU - Syafruddin, Din
AU - Matsuoka, Hiroyuki
AU - Matsuzaki, Motomichi
AU - Toyama, Tomoko
AU - Sturm, Angelika
AU - Cozijnsen, Anton
AU - Jacobs-Lorena, Marcelo
AU - Kita, Kiyoshi
AU - Marzuki, Sangkot
AU - McFadden, Geoffrey I.
N1 - Publisher Copyright:
© 2016, American Association for the Advancement of Science. All rights reserved.
PY - 2016/4/15
Y1 - 2016/4/15
N2 - 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.
AB - 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.
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U2 - 10.1126/science.aad9279
DO - 10.1126/science.aad9279
M3 - Article
C2 - 27081071
AN - SCOPUS:84963727426
SN - 0036-8075
VL - 352
SP - 349
EP - 353
JO - Science
JF - Science
IS - 6283
ER -