Plasmodium knowlesi exhibits distinct in vitro drug susceptibility profiles from those of Plasmodium falciparum

Publication date: Available online 22 February 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Donelly A. van Schalkwyk, Benjamin Blasco, Rocio Davina Nuñez, Jonathan W.K. Liew, Amirah Amir, Yee L. Lau, Didier Leroy, Robert W. Moon, Colin J. SutherlandAbstractNew antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P. falciparum. We compared the in vitro susceptibility of P. knowlesi and P. falciparum to a range of established and novel antimalarial agents under identical assay conditions. We demonstrated that P. knowlesi is significantly less susceptible than P. falciparum to six of the compounds tested; and notably these include three ATP4 inhibitors currently under development as novel antimalarial agents, and one investigational antimalarial, AN13762, which is 67 fold less effective against P. knowlesi. For the other compounds there was a less than two-fold difference in susceptibility between species. ...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research