Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum

Chavchich, Marina, Gerena, Lucia, Peters, Jennifer, Chen, Nanhua, Cheng, Qin and Kyle, Dennis E. (2010) Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum. Antimicrobial Agents and Chemotherapy, 54 6: 2455-2464. doi:10.1128/AAC.00947-09

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Author Chavchich, Marina
Gerena, Lucia
Peters, Jennifer
Chen, Nanhua
Cheng, Qin
Kyle, Dennis E.
Title Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum
Formatted title
Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
1098-6596
Publication date 2010-01-01
Sub-type Article (original research)
DOI 10.1128/AAC.00947-09
Open Access Status File (Publisher version)
Volume 54
Issue 6
Start page 2455
End page 2464
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
Artemisinin and its derivatives are the most rapidly acting and efficacious antimalarial drugs currently available. Although resistance to these drugs has not been documented, there is growing concern about the potential for resistance to develop. In this paper we report the selection of parasite resistance to artelinic acid (AL) and artemisinin (QHS) in vitro and the molecular changes that occurred during the selection. Exposure of three Plasmodium falciparum lines (W2, D6, and TM91C235) to AL resulted in decreases in parasite susceptibilities to AL and QHS, as well as to mefloquine, quinine, halofantrine, and lumefantrine. The changes in parasite susceptibility were accompanied by increases in the copy number, mRNA expression, and protein expression of the pfmdr1 gene in the resistant progenies of W2 and TM91C235 parasites but not in those of D6 parasites. No changes were detected in the coding sequences of the pfmdr1, pfcrt, pfatp6, pftctp, and pfubcth genes or in the expression levels of pfatp6 and pftctp. Our data demonstrate that P. falciparum lines have the capacity to develop resistance to artemisinin derivatives in vitro and that this resistance is achieved by multiple mechanisms, to include amplification and increased expression of pfmdr1, a mechanism that also confers resistance to mefloquine. This observation is of practical importance, because artemisinin drugs are often used in combination with mefloquine for the treatment of malaria.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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Created: Tue, 25 Oct 2011, 23:12:06 EST by Geraldine Fitzgerald on behalf of School of Public Health