Genomics strategy for rapid identification of mutations associated with drug resistance in malaria parasites

Abstract

Malaria caused by Plasmodium falciparum represents one of the leading causes of child mortality in tropical and subtropical regions. Because no vaccine is available, treatment-based case management is the primary option for malaria control. However, over time, P. falciparum parasites have evolved resistance to all available drugs. Our group has developed a novel paradigm that brings together principles of classical genetics and innovative concepts of genomics, in order to understand the genetic and molecular basis of resistance to antimalarials. This strategy makes use of an isogenic lineage of the rodent parasite Plasmodium chabaudi, consisting of various clones that are either sensitive or resistant to different drugs, whose genomes are scrutinized in search for mutations responsible drug resistance. Using this strategy, the genetic basis of resistance to various antimalarials, such as pyrimethamine, chloroquine, mefloquine and artemisinin, has been clarified.