Knowing one’s enemy: the Plasmodium parasite

There are five species of Plasmodium that infect humans, of which the most serious is Plasmodium falciparum. Genetic studies have been useful in determining the biosynthetic pathways that take place within the parasite, and in identifying potential drug targets for potential novel antimalarial drugs. The life cycle of the parasite is complex, involving two hosts and various asexual and sexual stages. Within the human host, the parasite infects liver cells and red blood cells. Antimalarial drugs that are currently of use in the clinic include quinolines, naphthoquinones, acryl alcohols, antifolates, antibiotics, and artemisinins. However, drug resistance is a growing problem and is a result of genetic mutations to current drug targets or drug transporters. Consequently, there has been rowing interest in developing novel antimalarial agents that act on other Plasmodium proteins such as the proteases involved in hemoglobin degradation or the enzymes that are involved in biosynthetic pathways occurring in the parasite’s apicoplast or mitochondria. Other potential drug targets include protein kinases, transferases, transporters, amino-acid tRNA synthetases, histone deacetylase, molecular chaperones, and drug transporters.