By Gene Yang ’19

Over 216 million cases of malaria, a disease caused by the Plasmodium parasite and transmitted by mosquitos, were recorded in 2016. While this disease still results in an estimated half a million deaths per year, the majority of which occurs in Sub-Saharan Africa, mortality rates are on the decline thanks to increased prevention and control. However, if malaria eradication is to succeed, new antimalarial drugs may be needed in the near future—Artemisinin was discovered in 2015 and quickly became the standard treatment, yet resistance to this medication has already been found in Southeast Asian malarial strains.

Dr. Annie Cowell and her team of researchers from the University of California San Diego and Washington University have made a step forward in the search for new antimalarial drugs using a type of study known as experimental evolution. Experimental evolution involves observing how microbial populations evolve over thousands of generations in a controlled setting. In this experiment, the malaria parasite P. falciparum was exposed to 37 diverse compounds with antimalarial properties for six months. As the population grew, it gradually developed resistance to these compounds.

To gain insight into resistance-induced genetic changes and new potential drugs target sites. Large-scale genome sequencing was then performed on 240 bacteria genomes. The comparison of “normal” P. falciparum to resistant P. falciparum found changes in 83 genes associated with drug-resistance. This included a mutation in the forkhead-associated domain of an uncharacterized protein, a region traditionally believed to be conserved. Additionally, potential drug target sites were also discovered. These novel target sites, which include thymidylate synthase and farnesyltransferase, are molecular structures that can potentially be targeted to kill the parasite. This finding allows the possibility of new classes of antimalarial drugs to be researched, leading one step closer to eliminating malaria entirely.

References

1. A. Cowell, et al., Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics. Science 359 (191-199). doi: 10.1126/science.aan4472.
2. Image retrieved from: https://upload.wikimedia.org/wikipedia/commons/d/da/Anopheles_minimus.jpg