Topics : Organisms : Group : Name of Applicant :
Didier Menard Date of application :
26-07-2018 Unit :
Biology of Host-parasite Interactions Location :
Nicolle build - 2nd floor Phone :
+33 1 44 38 91 35@ Mail :
Project context and summary :
We are involved, in collboration with the WHO, in the SaMARA which aims at detecting the emergence of antimalarial drug resistance in Africa.
Samples (dried blood spots) are collected from the Nantional Malaria Control Programmes in Africa during clinical efficacy studies. My group at the Institut Pasteur in collaboration with the Institut Cochin (Frédéric Ariey) tested these samples and assessed the proportion of parasites harboring SNPs or CNV associated to antimalarial drug resistance.
We have previously demonstrated that mutations in the propeller dommain of a Kelch gene located on the chromosome 13 are strongly predictive of artemsinin resistance.
Until last year, artemisinin resistance was confined in South east Asia. Recently, we have detected in African samples a high proportion of mutant parasites. This mutation has never been observed before in South east Asia. To perform comprenhensive genomic analysis, we have sequenced (Illumina) all mutants (=24) and paired wild type samples.
Analysis of these sequences (and 400 whole genome sequences from parasites collected in Asia, Africa and America, upload on a dedicated website) should allow to:
- define if the mutants have emerged locally or have spread from Asia
- define the genetic background of these mutants (are specific alleles facilitated the emergence of K13 mutantions)
- describe the genomic profile(s) of these mutants (especially the haplotypes associated to multidrug resistance)Related team publications :
Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, Kim S, Duru V, Bouchier C, Ma L, Lim P, Leang R, Duong S, Sreng S, Suon S, Chuor CM, Bout DM, Menard S, Rogers WO, Genton B, Fandeur T, Miotto O, Ringwald P, Le Bras J, Berry A, Barale JC, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, & Menard D (2014) A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505(7481):50-55
Straimer J, Gnadig NF, Witkowski B, Amaratunga C, Duru V, Ramadani AP, Dacheux M, Khim N, Zhang L, Lam S, Gregory PD, Urnov FD, Mercereau-Puijalon O, Benoit-Vical F, Fairhurst RM, Menard D, & Fidock DA (2015) Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 347(6220):428-431.
Menard D, Khim N, Beghain J, Adegnika AA, Shafiul-Alam M, Amodu O, Rahim-Awab G, Barnadas C, Berry A, Boum Y, Bustos MD, Cao J, Chen JH, Collet L, Cui L, Thakur GD, Dieye A, Djalle D, Dorkenoo MA, Eboumbou-Moukoko CE, Espino FE, Fandeur T, Ferreira-da-Cruz MF, Fola AA, Fuehrer HP, Hassan AM, Herrera S, Hongvanthong B, Houze S, Ibrahim ML, Jahirul-Karim M, Jiang L, Kano S, Ali-Khan W, Khanthavong M, Kremsner PG, Lacerda M, Leang R, Leelawong M, Li M, Lin K, Mazarati JB, Menard S, Morlais I, Muhindo-Mavoko H, Musset L, Na-Bangchang K, Nambozi M, Niare K, Noedl H, Ouedraogo JB, Pillai DR, Pradines B, Quang-Phuc B, Ramharter M, Randrianarivelojosia M, Sattabongkot J, Sheikh-Omar A, Silue KD, Sirima SB, Sutherland C, Syafruddin D, Tahar R, Tang LH, Toure OA, Tshibangu-wa-Tshibangu P, Vigan-Womas I, Warsame M, Wini L, Zakeri S, Kim S, Eam R, Berne L, Khean C, Chy S, Ken M, Loch K, Canier L, Duru V, Legrand E, Barale JC, Stokes B, Straimer J, Witkowski B, Fidock DA, Rogier C, Ringwald P, Ariey F, Mercereau-Puijalon O, & Consortium K (2016) A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms. N Engl J Med 374(25):2453-2464..