Functional analysis of drug resistance in Plasmodium falciparum in the post-genomic era

Malaria has plagued humans throughout recorded history and results in the death of over 2 million people per year. The protozoan parasite Plasmodium falciparum causes the most severe form of malaria in humans. Chemotherapy has become one of the major control strategies for this parasite; however, the development of drug resistance to virtually all of the currently available drugs is causing a crisis in the use and deployment of these compounds for prophylaxis and treatment of this disease. The genome sequence of P. falciparum is providing the informational base for the use of whole-genome strategies such as bioinformatics, microarrays and genetic mapping. These approaches, together with the availability of a high-resolution genome linkage map consisting of hundreds of microsatellite markers and the advanced technologies of transfection and proteomics, will facilitate an integrated approach to address important biological questions. In this review we will discuss strategies to identify novel genes involved in the molecular mechanisms used by the parasite to circumvent the lethal effect of current chemotherapeutic agents.