Decreasingpfmdr1Copy Number inPlasmodium falciparumMalaria Heightens Susceptibility to Mefloquine, Lumefantrine, Halofantrine, Quinine, and Artemisinin

• DOI: 10.1086/507115
• Publication Date: 2006-07-25T11:22:50Z
• Authors: Amar Bir Singh Sidhu; Anne‐Catrin Uhlemann; Stephanie G. Vald...; Juan‐Carlos Valde...; Sanjeev Krishna; David A. Fidock
• Keywords: Halofantrine; Quinine; Lumefantrine; Artesunate; Artemether

The global dissemination of drug-resistant Plasmodium falciparum is spurring intense efforts to implement artemisinin (ART)–based combination therapies for malaria, including mefloquine (MFQ)–artesunate and lumefantrine (LUM)–artemether. Clinical studies have identified an association between increased risk MFQ, MFQ-artesunate, LUM-artemether treatment failures pfmdr1 gene amplification. To directly address the contribution that copy number makes drug resistance, we genetically disrupted 1 2 copies in FCB line, which resulted reduced mRNA protein expression. These knockdown clones manifested a 3-fold decrease MFQ IC50 values, compared with verifying role played by expression levels mediating resistance MFQ. also showed susceptibility LUM, halofantrine, quinine, ART. No change was observed chloroquine. results highlight importance determining P. multiple agents currently being used combat malaria caused multidrug-resistant parasites