2016
DOI: 10.1038/srep33891
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Genome-wide association analysis identifies genetic loci associated with resistance to multiple antimalarials in Plasmodium falciparum from China-Myanmar border

Abstract: Drug resistance has emerged as one of the greatest challenges facing malaria control. The recent emergence of resistance to artemisinin (ART) and its partner drugs in ART-based combination therapies (ACT) is threatening the efficacy of this front-line regimen for treating Plasmodium falciparum parasites. Thus, an understanding of the molecular mechanisms that underlie the resistance to ART and the partner drugs has become a high priority for resistance containment and malaria management. Using genome-wide asso… Show more

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Cited by 80 publications
(86 citation statements)
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“…Mutations in this gene were also found in loops between transmembrane domains and were associated with resistance to three diverse compounds: MMV007224 (-135I inframe insertion), MMV668399 (P380S, K238N, V185L), and MMV011895 ((F230L). This gene was found to be associated with levels of chloroquine resistance in P. falciparum in a genomewide association study (38), and we found that the product of pfaat1 localizes to the P. falciparum digestive vacuole ( Figure S4). Thus, the amino transporter encoded by pfaat1 may play a role in efflux of multiple drugs from the digestive vacuole, similar to PfCRT.…”
Section: Discovery Of New Alleles In Known Drug Resistance Genesmentioning
confidence: 87%
See 1 more Smart Citation
“…Mutations in this gene were also found in loops between transmembrane domains and were associated with resistance to three diverse compounds: MMV007224 (-135I inframe insertion), MMV668399 (P380S, K238N, V185L), and MMV011895 ((F230L). This gene was found to be associated with levels of chloroquine resistance in P. falciparum in a genomewide association study (38), and we found that the product of pfaat1 localizes to the P. falciparum digestive vacuole ( Figure S4). Thus, the amino transporter encoded by pfaat1 may play a role in efflux of multiple drugs from the digestive vacuole, similar to PfCRT.…”
Section: Discovery Of New Alleles In Known Drug Resistance Genesmentioning
confidence: 87%
“…Our study represents one of the most comprehensive and controlled studies of antimalarial drug resistance acquisition by P. falciparum to date. Prior studies examining the parasite's genetic response during drug resistance development have evaluated the response to known antimalarials only (38,45,60,61), or have focused on coding mutations in one target gene in reponse to a single compound class (4)(5)(6)(7)(8)(9)(10)39). It is likely that the genes that are identified here will prove important to both clinical studies and the process of drug development.…”
Section: Discussionmentioning
confidence: 99%
“…In yeast, Atg2 establishes a complex with Atg9 (a 6 transmembrane domains protein) and Atg18 (a phosphatidylinositol triphosphate binding protein) and is involved in the formation of pre‐autophagosomal structure during the preliminary step of autophagy (Tanida, , Hain & Bosch, ). A homologue of Atg18 has been identified in P. falciparum (PF3D7_1012900), and it has recently been shown to be critical for the inheritance of the apicoplast (Bansal et al, ; Wang et al, ). Of note, PfAtg18 was not found in our list of GP1 interacting proteins.…”
Section: Discussionmentioning
confidence: 99%
“…Another autophagy protein, Pf ATG18, is also reported to be involved in the apicoplast biogenesis and is shown to mediate the localisation of Pf ATG8 to the apicoplast membrane (Bansal, Tripathi, Thakur, Mohmmed, & Sharma, ). A single nucleotide polymorphism (SNP) in the Pf ATG18 gene is associated with artemisinin resistance in the clinical isolates (Miotto et al, ; Wang et al, ), which also promotes the survival of the parasite under limited nutrient conditions (Breglio et al, ). In this study, we sought to decipher the functions of Pf ATG18 in more detail.…”
Section: Introductionmentioning
confidence: 99%