A broad analysis of resistance development in the malaria parasite

• DOI: 10.1038/ncomms11901
• Publication Date: 2016-06-15T17:14:38Z
• Authors: Victoria C. Corey; Amanda K. Lukens; Eva S. Istvan; Marcus C. S. Lee; Virginia Franco; Pamela Magistrado; Olivia Coburn-Flynn; Tomoyo Sakata-Kato; Olivia Fuchs; Nina F. Gnädig; Greg Goldgof; Maria Linares; Maria G. Gomez-Lo...; Cristina De Cózar; Maria Jose Lafuen...; Sara Prats; Stephan Meister; Olga Tanaseichuk; Melanie Wree; Yingyao Zhou; Paul A. Willis; Francisco-Javier ...; Daniel E. Goldberg; David A. Fidock; Dyann F. Wirth; Elizabeth A. Winz...
• Keywords: 0301 basic medicine; 24 Ciencias de la Vida; Science; Plasmodium falciparum; Drug Resistance; Polymorphism, Single Nucleotide; 630; Article; Antimalarials; 03 medical and health sciences; INDEL Mutation; name=General Biochemistry,Genetics and Molecular Biology; 616; Animals; Parasites; /dk/atira/pure/subjectarea/asjc/1300/1300; Q; Clone Cells; 3. Good health; Ciencias Biomédicas; name=General Physics and Astronomy; Mutation; /dk/atira/pure/subjectarea/asjc/3100/3100; name=General Chemistry; /dk/atira/pure/subjectarea/asjc/1600/1600

Abstract Microbial resistance to chemotherapy has caused countless deaths where malaria is endemic. Chemotherapy may fail either due pre-existing or evolution of drug-resistant parasites. Here we use a diverse set antimalarial compounds investigate the acquisition drug and degree cross-resistance against common alleles. We assess using 15 parasite lines carrying resistance-conferring alleles in pfatp4 , cytochrome bc 1 pfcarl pfdhod, pfcrt pfmdr, pfdhfr, cytoplasmic prolyl t-RNA synthetase hsp90 . Subsequently, whether resistant parasites can be obtained after several rounds selection. Twenty-three 48 vitro selections result parasites, with time onset ranging from 300 days. Our data indicate that not major hurdle for novel-target candidates, focusing our attention on fast-killing slower clinical resistance.