131: pBI143: The Human Gut’s Hidden Heavyweight

️ Episode 131: pBI143: The Human Gut’s Hidden Heavyweight In this episode of PaperCast Base by Base, we explore how a tiny 2.7 kb cryptic plasmid, pBI143, emerges as one of the most numerous genetic elements in industrialized human gut microbiomes, mobilizes across Bacteroidales, persists as monoclonal lineages with vertical transmission, and increases its copy number under stress and in inflammatory bowel disease. Study Highlights:The authors surveyed 4,516 globally distributed gut metagenomes and found that the 2.7 kb plasmid pBI143 is highly prevalent in industrialized populations and, when normalized by genome size, is on average at least fourteen times more numerous than crAssphage. Isolate screening and conjugation assays showed transfer between Bacteroidales species, while single‑nucleotide‑variant profiling revealed largely monoclonal populations within individuals and frequent vertical transmission from mothers to infants. In gnotobiotic mice, pBI143 imposed a small fitness cost on Bacteroides fragilis, yet metagenomic assemblies occasionally captured larger pBI143 variants bearing cargo genes that could benefit hosts and suggest a natural shuttle vector. Copy‑number measurements increased under oxidative stress in vitro and were significantly higher in metagenomes from individuals with inflammatory bowel disease, and a qPCR assay demonstrated pBI143’s sensitivity and specificity as a marker of human fecal contamination. Conclusion:Together these findings position pBI143 as a human-specific, ultra-abundant mobile element that serves as a sensitive biomarker of gut stress and contamination while offering a natural backbone for payload delivery in the microbiome. Reference:Fogarty EC, Schechter MS, Lolans K, Sheahan ML, Veseli I, Moore RM, Kiefl E, Moody T, Rice PA, Yu MK, Mimee M, Chang EB, Ruscheweyh H‑J, Sunagawa S, McLellan SL, Willis AD, Comstock LE, Eren AM. A cryptic plasmid is among the most numerous genetic elements in the human gut. Cell. 2024;187(5):1206–1222. https://doi.org/10.1016/j.cell.2024.01.039 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:If you'd like to support Base by Base, you can make a one-time or monthly donation here: https://basebybase.castos.com/

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