%0 Journal Article
%A Corey, Victoria
%A Lukens, Amanda
%A Istvan, Eva
%A Lee, Marcus
%A Franco, Virginia
%A Magistrado, Pamela
%A Coburn-Flynn, Olivia
%A Sakata-Kato, Tomoyo
%A Fuchs, Olivia
%A Gnädig, Nina
%A Goldgof, Greg
%A Linares Gómez, María
%A Gomez-Lorenzo, Maria 
%A Cózar, Cristina De
%A Lafuente-Monasterio, Maria Jose
%A Prats, Sara
%A Meister, Stefan
%A Tanaseichuk, Olga
%A Wree, Melanie
%A Zhou, Yingyao 
%A Willis, Paul
%A Gamo, Francisco-Javier
%A Goldberg, Daniel
%A Fidock, David
%A Wirth, Dyann
%A Winzeler, Elizabeth
%T A broad analysis of resistance development in the malaria parasite
%D 2016
%@ 2041-1723
%U https://hdl.handle.net/20.500.14352/93533
%X Microbial resistance to chemotherapy has caused countless deaths where malaria is endemic. Chemotherapy may fail either due to pre-existing resistance or evolution of drug-resistant parasites. Here we use a diverse set of antimalarial compounds to investigate the acquisition of drug resistance and the degree of cross-resistance against common resistance alleles. We assess cross-resistance using a set of 15 parasite lines carrying resistance-conferring alleles in pfatp4, cytochrome bc1, pfcarl, pfdhod, pfcrt, pfmdr, pfdhfr, cytoplasmic prolyl t-RNA synthetase or hsp90. Subsequently, we assess whether resistant parasites can be obtained after several rounds of drug selection. Twenty-three of the 48 in vitro selections result in resistant parasites, with time to resistance onset ranging from 15 to 300 days. Our data indicate that pre-existing resistance may not be a major hurdle for novel-target antimalarial candidates, and focusing our attention on fast-killing compounds may result in a slower onset of clinical resistance.
%~