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Nature Papers on Method to Help Complete Metagenome-Assembled Genomes, Optogenetic Control of Gene Editing, More

A new method that combines deep sequencing using long (HiFi) reads with Hi-C binning can help overcome challenges facing the generation of complete metagenome-assembled genomes (MAGs) from complex microbial communities, a team led by US Department of Agriculture scientists reports in Nature Biotechnology this week. The creation of reference-quality, species-level assemblies from metagenome communities is challenging since microbial communities often contain distinct lineages of closely related organisms. In the study, the researchers used HiFi sequencing to sequence the sheep fecal metagenome, identifying 428 MAGs with more than 90 percent completeness. To resolve closely related strains, they developed MAGPhase, a computational method that separates lineages of related organisms by discriminating variant haplotypes across hundreds of kilobases of genomic sequence, which they use to identify 220 lineage-resolved MAGs in their dataset. "Lineage-resolved complete MAGs are a step toward complete metagenomics — isolate-quality genome assemblies for microbial organisms from complex metagenome samples," they write.

A light-based system for controlling RNA function and metabolism that can also be applied to CRISPR genome editing is described in Nature Biotechnology this week. RNA-binding proteins (RBPs) are key to regulating RNA function in the cell but controlling RBP activity is difficult. To address this, investigators from East China University of Science and Technology developed a photoswitchable RBP, dubbed LicV, that binds to a specific RNA sequence in response to blue light irradiation. By fusing LicV to different RNA effectors, the scientists could control RNA localization, splicing, translation, and stability in cell culture. They also describe a LicV-assisted CRISPR-Cas9 system called LA-CRISPR that enables efficient and tunable photoswitchable regulation of transcription and genomic locus labeling. "LA-CRISPR," they write, "will allow for the realization of … applications such as the optogenetic control of gene silencing, genome editing, and the control and imaging of endogenous RNAs."

While the clinical use of antibiotics is believed to be a major cause of antibiotic resistance, a new study appearing in Nature shows that methicillin-resistant Staphylococcus aureus (MRSA) appeared in hedgehogs in the pre-antibiotic era. MRSA was first identified in 1960 shortly after the introduction of methicillin as a treatment option for penicillin-resistant S. aureus. Methicillin resistance has subsequently emerged in many S. aureus clones around the world, within healthcare settings as well as in livestock. In the study, a team led by scientists from the Statens Serum Institut sequenced hundreds of S. aureus isolates from hedgehogs and other sources, revealing that MRSA was present in the animals in Europe prior to the development of antibiotics, after which it spread within the local hedgehog populations and between hedgehogs and secondary hosts including humans and animals. The findings challenge the commonly accepted view that widespread resistance in clinical pathogens is a modern phenomenon driven by use of antibiotics in human and veterinary medicine, underscoring the importance of taking a broad One Health perspective on antibiotic resistance that recognizes the role of natural selection in wild animals and the connectivity of natural, agricultural, and human ecosystems in the evolution and spread of antibiotic-resistant pathogens, the scientists write.