Details

Autor(en) / Beteiligte

• Corey, Victoria C
• Lukens, Amanda K
• Istvan, Eva S
• Lee, Marcus C S
• Franco, Virginia
• Magistrado, Pamela
• Coburn-Flynn, Olivia
• Sakata-Kato, Tomoyo
• Fuchs, Olivia
• Gnädig, Nina F
• Goldgof, Greg
• Linares, Maria
• Gomez-Lorenzo, Maria G
• De Cózar, Cristina
• Lafuente-Monasterio, Maria Jose
• Prats, Sara
• Meister, Stephan
• Tanaseichuk, Olga
• Wree, Melanie
• Zhou, Yingyao
• Willis, Paul A
• Gamo, Francisco-Javier
• Goldberg, Daniel E
• Fidock, David A
• Wirth, Dyann F
• Winzeler, Elizabeth A

Titel

A broad analysis of resistance development in the malaria parasite

Ist Teil von

• Nature communications, 2016-06, Vol.7 (1), p.11901-11901, Article 11901

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.