The genomic architecture of antimalarial drug resistance

• Published in: Briefings in functional genomics Vol. 18; no. 5; pp. 314 - 328
• Main Authors: Cowell, Annie N, Winzeler, Elizabeth A
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 24.09.2019
• Subjects: Aminoquinolines - therapeutic use; Anti-Bacterial Agents - therapeutic use; Antimalarials - therapeutic use; Artemisinins - therapeutic use; Atovaquone - therapeutic use; Drug Resistance - genetics; Drug Resistance, Multiple - genetics; Folic Acid Antagonists - therapeutic use; Humans; Malaria - drug therapy; Plasmodium falciparum - genetics; Plasmodium falciparum - growth & development; Plasmodium falciparum - pathogenicity; Plasmodium vivax - genetics; Plasmodium vivax - growth & development; Plasmodium vivax - pathogenicity; Quinine - therapeutic use; Review Paper; artemisinin; Plasmodium falciparum; Plasmodium vivax; drug resistance; malaria
• ISSN: 2041-2657; 2041-2649; 2041-2657
• DOI: 10.1093/bfgp/elz008

Plasmodium falciparum and Plasmodium vivax, the two protozoan parasite species that cause the majority of cases of human malaria, have developed resistance to nearly all known antimalarials. The ability of malaria parasites to develop resistance is primarily due to the high numbers of parasites in the infected person’s bloodstream during the asexual blood stage of infection in conjunction with the mutability of their genomes. Identifying the genetic mutations that mediate antimalarial resistance has deepened our understanding of how the parasites evade our treatments and reveals molecular markers that can be used to track the emergence of resistance in clinical samples. In this review, we examine known genetic mutations that lead to resistance to the major classes of antimalarial medications: the 4-aminoquinolines (chloroquine, amodiaquine and piperaquine), antifolate drugs, aryl amino-alcohols (quinine, lumefantrine and mefloquine), artemisinin compounds, antibiotics (clindamycin and doxycycline) and a napthoquinone (atovaquone). We discuss how the evolution of antimalarial resistance informs strategies to design the next generation of antimalarial therapies.