Challenging Malaria Control

HIRAI MAKOTO, MITA TOSHIHIRO

doi:10.14789/jmj.61.370

Malaria is caused by the Plasmodium genus in the phylum Apicomplexa, and P. falciparum is the most malignant parasite species. Because the malaria parasite possesses antigenic variation through a variety of gene families, it can evade human immune surveillance, which makes vaccine development difficult. In addition, the parasite quickly acquires drug resistance/tolerance to existing antimalarial drugs by mutating its genome and changing its gene expression levels. In this context, there is no effective vaccine or drug available for malaria control. In 2002, sequencing of P. falciparum genome was completed and it appears that approximately 5,300 genes are coded in its genome, of which 60% have unknown function. Because genetic manipulations such as knock-in, knockout and the transient expression of foreign genes are applicable to the Plasmodium species, we anticipate that understanding of the parasite biology will be accelerated and that the accumulated knowledge will soon lead to identification of new vaccine targets or drugs. However, the malaria burden still threatens human life because the current genetic tools are not sufficient to unravel Plasmodium biology; thus, novel genetic tools are necessary. Recently, we have succeeded in the creation of “malaria mutator”. Malaria mutator showed a mutation rate that was 80 times higher than that of the wild-type parasite. We readily isolated drug-resistant parasites from the malaria mutator library in a few rounds of screening. Whole-genome sequencing and subsequent single nucleotide polymorphism (SNP) analysis identified candidate causative gene mutations for drug resistance. In this review, we introduce our malaria mutator and discuss its usefulness for Plasmodium biology research compared with conventional tools. We describe our recent attempt to deepen our understanding of Plasmodium biology, including drug resistance and immune evasion by using malaria mutator.

Challenging Malaria Control

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