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PNAS Papers on TB in Tibet, Chemo-Induced Stress in Multiple Myeloma, Wasp Symbiont

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted this week.

Researchers from Fudan University's Shanghai Institute of Infectious Disease and Biosecurity and elsewhere report on Mycobacterium tuberculosis adaptations found at high-altitude sites in the Tibetan Plateau. With comparative and phylogenomic analyses on nearly 600 whole-genome sequenced M. tuberculosis samples collected in seven municipal regions in Tibet over three different years — in 2006, 2009, and 2010 — the team found that tuberculosis pathogens in the region have remained isolated from those found at lower altitude sites in China, becoming locally adapted along the way. "Our study found that the Mtb strains currently circulating in the Tibetan Plateau were introduced repeatedly into the region between the [18th] and [20th] century and then diversified locally while remaining geographically isolated from the Mtb strains in the plain regions of China," the authors report, noting that "isolation made is possible to document evidence that local selection has shaped the evolution of the Mtb strains on the Tibetan Plateau."

An Imperial College London-led team looks at mechanisms that multiple myeloma cells use to bounce back from chemotherapy-related stress. After exposing multiple myeloma cells to a proteasome inhibitor called carfilzomib in vitro, the researchers tracked RNA sequence data, tandem mass tag-based quantitative proteome profiles, and metabolomic patterns assessed with liquid chromatography-tandem mass spec analyses over time, uncovering stress response mechanisms marked by lower-than-usual levels of mitochondrial activity and shifts in metabolic pathways involved in glucose and lipid use. Their results also hint at the possibility of targeting an amino acid-related kinase enzyme encoded by GCN2 in a subset of multiple myeloma cells sharing a transcriptome signature with some solid cancers. "Using a temporal multi-omics approach, we delineate the unexpectedly complex and protracted changes myeloma cells are more vulnerable to specific insults than acutely stressed cells," they write, noting that "the findings may provide avenues for optimizing cancer therapies."

Investigators in Germany and the US take a look at Streptomyces bacteria that act as symbionts in the European beewolf wasp Philanthus triangulum. The team used a combination of short- and long-read genome sequencing — along with RNA sequencing and liquid chromatography-mass spec-based proteomic profiling — to characterize the S. philanthi biovar triangulum, comparing it to free-living Streptomyces and to symbionts found in other beewolf species. Together with functional clues, these data indicated that the P. triangulum symbiont has a slimmed down genome that includes metabolic pathways that integrate host and symbiont features to produce antibiotics and other defensive products. "Our results show unusual traits in the early stage of genome erosion in a defensive symbiont and suggest tight integration of host-symbiont metabolic pathways that effectively grants the host control over the antimicrobial activity of its bacterial partner," the authors suggest.