RT Journal Article
T1 A broad analysis of resistance development in the malaria parasite
A1 Corey, Victoria
A1 Lukens, Amanda
A1 Istvan, Eva
A1 Lee, Marcus
A1 Franco, Virginia
A1 Magistrado, Pamela
A1 Coburn-Flynn, Olivia
A1 Sakata-Kato, Tomoyo
A1 Fuchs, Olivia
A1 Gnädig, Nina
A1 Goldgof, Greg
A1 Linares Gómez, María
A1 Gomez-Lorenzo, Maria
A1 Cózar, Cristina De
A1 Lafuente-Monasterio, Maria Jose
A1 Prats, Sara
A1 Meister, Stefan
A1 Tanaseichuk, Olga
A1 Wree, Melanie
A1 Zhou, Yingyao
A1 Willis, Paul
A1 Gamo, Francisco-Javier
A1 Goldberg, Daniel
A1 Fidock, David
A1 Wirth, Dyann
A1 Winzeler, Elizabeth
AB 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.
PB Nature Research
SN 2041-1723
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/93533
UL https://hdl.handle.net/20.500.14352/93533
LA eng
NO Corey VC, Lukens AK, Istvan ES, Lee MCS, Franco V, Magistrado P, et al. A broad analysis of resistance development in the malaria parasite. Nat Commun 2016;7:11901. https://doi.org/10.1038/ncomms11901.
NO Bill and Melinda Gates Foundation
NO National Institute of Allergy and Infectious Diseases
NO University of California 
NO National Institute of General Medical Sciences
DS Docta Complutense
RD 6 abr 2025