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Malaria Gene Targets Lit Up

Scientists have developed a new technique to investigate the effects of gene deletion at later stages in the life cycle of the parasite that causes malaria. New treatments are needed for malaria because of increasing drug resistance in the single-celled Plasmodium parasites that cause it.

The new study, published in PLOS Pathogens, focused on the ferrochelatase (FC) gene in Plasmodium berghei, which causes malaria in rodents and is commonly used in mouse studies of malaria. The FC gene allows P. berghei to produce heme, which is essential for P. berghei development in the mosquitoes that transmit the parasite between rodent hosts, but is not essential during a later stage in the rodent bloodstream. However, between these two stages, P. berghei undergoes a developmental phase in the rodent liver, and it has been unclear whether heme synthesis is essential at this stage.

Upeksha Rathnapala and colleagues at The University of Melbourne produced P. berghei parasites that are capable of expressing the FC gene and developing properly in mosquitoes, but produce a mix of FC-expressing and FC-deficient parasites once they infect mouse liver cells. The scientists genetically engineered the parasites so that FC-deficient individuals would express fluorescent markers that allowed easy identification.

The researchers found that FC-deficient parasites were unable to complete their liver development phase. This suggests that disrupting the heme synthesis pathway could be an effective way to target Plasmodium parasites in the liver. Such an approach would be prevent the development of malaria, since symptoms aren’t apparent until the parasite leaves the liver and begins its bloodstream phase.

The researchers say that this novel approach involving fluorescent markers could be adapted for other genes, allowing scientists to identify additional metabolic processes that are essential for Plasmodium development in host animals.

“The idea of tagging mutant genes with fluorescent proteins is a simple one but it allowed us to follow mutant parasites throughout the malaria life cycle and dissect their phenotypes in the liver stage, something that hasn’t been easy to do for mutations that block mosquito development,” the authors explained. “Our analysis of heme biosynthesis shows the power of this simple method but it’s a technique that can be easily applied to other genes and other malaria parasite species, greatly expanding the scope for investigating this immunologically important stage in the malaria parasite’s life cycle.”