Thursday, January 11, 2018 -- Malaria remains a complicated global health problem that is on the precipice of a resurgence in areas where it has long since subsided if climate change continues its “heated” rise. Understanding the molecular mechanisms that allow this pervasive parasite to traverse multiple hosts could hold the key to disease elimination, or, at the very least, keeping outbreaks under control. Now, investigators at Penn State University (PSU) have uncovered that malaria parasites have not one, but two, specialized proteins that protect its messenger RNAs (mRNAs) until the parasite takes up residence in a new mosquito or a human host. Findings from the new study were published recently in mSphere in an article entitled “ Nuclear, Cytosolic, and Surface-Localized Poly(A)-Binding Proteins
Friday, January 12, 2018 -- The malaria parasite’s shifting defenses against antimalarial drugs have been shadowed by scientists on the lookout for new druggable targets. The scientists, led by researchers based at the University of California San Diego School of Medicine, used experimental evolution and whole-genome analysis to identify drug-resistance genes. The scientists conducted this work systematically, producing a map of the chemogenetic landscape that could guide the design of small-molecule inhibitors against the malaria parasite, which kills hundreds of thousands of people each year. Details of the work appeared January 12 in the journal Science, in an article entitled “Mapping the Malaria Parasite Druggable Genome by Using In Vitro Evolution and Chemogenomics.” This article describes how the scientists performed a genome analysis
Thursday, January 11, 2018 -- Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target–inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.