pfmdr1 (Plasmodium falciparum multidrug drug resistance gene 1): a pivotal factor in malaria resistance to artemisinin combination therapies

Abstract

Plasmodium falciparum, the deadly agent of malaria, is notorious for its capacity to develop drug resistance. Treatment failures of artemisinin therapy regimens (ACTc), the present mainstay, is emerging. The transporter coding pfmdr1 gene is a central node in this process, having been associated with in vitro and in vivo parasite response to a broad range of ACT antimalarials. Areas covered: The review covers the historical origins of the pfmdr1 discovery, followed by a detailed description of its sequence and expression characteristics, as well as the structural and functional characteristics of its coded transmembrane protein. pfmdr1 association with ACT drugs response in vivo and in vitro is thoroughly reviewed. A reference is made to significant compounds presently in the development pipeline. The literature search was focused on Pubmed based searches with occasional resource to edited books, World Health Organization documentation and conference reports for adding valuable details. Expert commentary: Pfmdr1 has emerged as the central gene in P. falciparum ACT resistance. Understanding the basis of this role is critical for epidemiologic surveillance and design of improved resistance-refractory antimalarials. Specifically, unveiling situations of drug collateral sensitivity associated with specific pfmdr1 genetic variation will provide opportunities for personalized optimal therapy options.

Keywords: ABC transporter; ACT; drug resistance; malaria; pfmdr1.