Scientists working on a common antimicrobial compound with antimalarial activity have discovered a range of new therapeutic strategies to combat malaria.
The research, published by Cell Press in the December 11th issue of the journal Cell Host and Microbe, provides valuable insight into how the human malaria parasite's requirement for fatty acids can be exploited as it progresses through the distinct stages of its complex life cycle.
Infection with the human malaria parasite, Plasmodium falciparum, begins when an infected mosquito bites a human. Injected parasites migrate to the liver where they copy themselves inside liver cells and prepare to enter the bloodstream, invading red blood cells and initiating the blood stages that cause the clinical manifestations of the disease.
P. falciparum changes and proliferates rapidly during these life stages and requires an abundant source of fatty acid molecules to build new cell membranes. Blood stage parasites synthesize fatty acids using a type II fatty acid biosynthesis (FAS-II) pathway that is also employed by bacteria. FAS-II had been viewed as an excellent therapeutic target in parasites and bacteria as it is distinct from the type I (FAS-I) pathway used by mammals.
The FAS-II inhibitor triclosan has been widely used in antimicrobial creams, lotions and soaps and is often present as an additive in plastics, textiles and implantable medical devices. Earlier studies identified FabI, an enzyme in the FAS-II pathway, as the predicted target of triclosan in malaria parasites, propelling extensive research efforts to develop novel antimalarials based on this compound.