Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes

被引：110

作者：

Goodman, Christopher D. ^{[1
]}

Siregar, Josephine E. ^{[1
,2
,6
]}

Mollard, Vanessa ^{[1
]}

Vega-Rodriguez, Joel ^{[3
]}

Syafruddin, Din ^{[2
,4
]}

Matsuoka, Hiroyuki ^{[5
]}

Matsuzaki, Motomichi ^{[6
]}

Toyama, Tomoko ^{[1
]}

Sturm, Angelika ^{[1
]}

Cozijnsen, Anton ^{[1
]}

Jacobs-Lorena, Marcelo ^{[3
]}

Kita, Kiyoshi ^{[6
,7
]}

Marzuki, Sangkot ^{[2
]}

McFadden, Geoffrey I. ^{[1
]}

机构：

[1] Univ Melbourne, Sch BioSci, Melbourne, Vic 3010, Australia

[2] Eijkman Inst Mol Biol, Jl Diponegoro 69, Jakarta 10430, Indonesia

[3] Johns Hopkins Univ, Malaria Res Inst, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA

[4] Hasanuddin Univ, Dept Parasitol, Fac Med, Jalan Perintis Kemerdekaan Km10, Makassar 90245, Indonesia

[5] Jichi Med Univ, Div Med Zool, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan

[6] Univ Tokyo, Grad Sch Med, Dept Biomed Chem, Bunkyo Ku, Tokyo 1130033, Japan

[7] Nagasaki Univ, Sch Trop Med & Global Hlth, Nagasaki 8528523, Japan

来源：

SCIENCE | 2016年 / 352卷 / 6283期

基金：

美国国家卫生研究院; 澳大利亚研究理事会; 英国医学研究理事会;

关键词：

FALCIPARUM CYTOCHROME-B; PLASMODIUM-BERGHEI; RODENT MALARIA; BC(1); INHERITANCE; METABOLISM; MUTATIONS; PROGUANIL; EMERGENCE; GENE;

D O I：

10.1126/science.aad9279

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：349 / 353

页数：5

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