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This Week in PNAS: Feb 13, 2018

Albert Einstein College of Medicine researchers explore genomic responses and potential resistance mechanisms in Plasmodium falciparum parasites exposed to compounds that block a nucleic acid synthesis step that is required in the malaria-causing protozoans but not in human cells. The team followed P. falciparum cultures treated with incrementally greater levels of a drug called DADMe-ImmG that inhibits a purine nucleoside phosphorylase (PfPNP) enzyme involved in a purine salvage step of nucleic acid synthesis. With genome sequencing on a handful of DADMe-ImmG-resistant clones, the authors linked decreasing drug response to rising PfPNP copy numbers, enhanced protein production, and/or mutations that altered phosphorylase sites that typically bind the drug. 

A University of Bern-led team takes a look at the machinery that makes it possible for the mitochondrial genome to segregate appropriately during cell division in the protozoan parasite Trypanosoma brucei, which has a lone kinetoplast carrying mitochondrial DNA on thousands of small plasmid-like circles. Using RNA interference and high-resolution microscopy, the researchers tracked the assembly of a tripartite attachment complex (TAC) that normally attaches kinetoplast DNA to parts of the flagella that help segregate DNA and explored the consequences of knocking out TAC components. For example, the authors note that the TAC "is assembled in a hierarchical order from the base of the flagellum toward the mitochondrial genome and that the assembly is not dependent on the [kinetoplast DNA] itself."

Researchers from Japan, Switzerland, Germany, and Israel characterize bacterial symbionts in the marine sponge Theonella swinhoei. The team focused on a Y chemotype of T. swinhoei from Japan that contains complex polyketide and peptide collections previously linked to filamentous symbiotic bacteria from the Candidatus species. To add to insights already obtained for Candidatus Entotheonella factor symbionts, the investigators used single-bacterial genome sequencing to characterize a symbiont called Candidatus Entotheonella serta, uncovering a large and diverse set of biosynthetic genes. "The data validate Entotheonella as a rich and varied producer taxon with considerable biotechnological potential," they write.