A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

被引：1447

作者：

Ariey, Frederic ^{[1
,2
]}

Witkowski, Benoit ^{[3
]}

Amaratunga, Chanaki ^{[4
]}

Beghain, Johann ^{[1
,2
]}

Langlois, Anne-Claire ^{[1
,2
]}

Khim, Nimol ^{[3
]}

Kim, Saorin ^{[3
]}

Duru, Valentine ^{[3
]}

Bouchier, Christiane ^{[5
]}

Ma, Laurence ^{[5
]}

Lim, Pharath ^{[3
,4
,6
]}

Leang, Rithea ^{[6
]}

Duong, Socheat ^{[6
]}

Sreng, Sokunthea ^{[6
]}

Suon, Seila ^{[6
]}

Chuor, Char Meng ^{[6
]}

Bout, Denis Mey ^{[7
]}

Menard, Sandie ^{[8
]}

Rogers, William O. ^{[9
]}

Genton, Blaise ^{[10
]}

Fandeur, Thierry ^{[1
,3
]}

Miotto, Olivo ^{[11
,12
,13
]}

Ringwald, Pascal ^{[14
]}

Le Bras, Jacques ^{[15
]}

Berry, Antoine ^{[8
]}

Barale, Jean-Christophe ^{[1
,2
]}

Fairhurst, Rick M. ^{[4
]}

Benoit-Vical, Franoise ^{[16
,17
]}

Mercereau-Puijalon, Odile ^{[1
,2
]}

Menard, Didier ^{[3
]}

机构：

[1] Inst Pasteur, Parasite Mol Immunol Unit, F-75724 Paris 15, France

[2] CNRS, URA 2581, F-75724 Paris 15, France

[3] Inst Pasteur Cambodge, Malaria Mol Epidemiol Unit, Phnom Penh, Cambodia

[4] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA

[5] Inst Pasteur, Dept Genomes & Genet, F-75724 Paris 15, France

[6] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia

[7] Natl Ctr Parasitol Entomol & Malaria Control, SSA WHO, Phnom Penh, Cambodia

[8] Ctr Hosp Univ Toulouse, Serv Parasitol & Mycol, F-31059 Toulouse 9, France

[9] Naval Med Res Unit 2 Detachment, Phnom Penh, Cambodia

[10] Swiss Trop & Publ Hlth Inst, CH-4051 Basel, Switzerland

[11] Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford OX3 7BN, England

[12] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand

[13] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[14] WHO, Global Malaria Program, CH-1211 Geneva, Switzerland

[15] CHU Bichat Claude Bernard, APHP, PRES Sorbonne Paris Cite, Ctr Natl Reference Paludisme, F-75018 Paris, France

[16] CNRS, Lab Chim Coordinat, UPR8241, F-31077 Toulouse 4, France

[17] Univ Toulouse, UPS, Inst Natl Polytech Toulouse, F-31077 Toulouse 4, France

来源：

NATURE | 2014年 / 505卷 / 7481期

基金：

英国惠康基金;

关键词：

KELCH-REPEAT SUPERFAMILY; IN-VITRO; PARASITE CLEARANCE; CHLOROQUINE RESISTANCE; ANTIMALARIAL-DRUGS; POINT MUTATIONS; SUSCEPTIBILITY; DISRUPTION; MEFLOQUINE; ARTESUNATE;

D O I：

10.1038/nature12876

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：

Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.

引用

页码：50 / +

页数：18

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