Biogenesis of DNA-carrying extracellular vesicles by the dominant human gut methanogenic archaeon

Abstract Extracellular vesicles (EVs) play many important roles in cells from all domains of life. Here, we characterize EVs produced by Methanobrevibacter smithii, the dominant methanogenic archaeon in the human gut, which contains a peptidoglycan cell wall. We show that M. smithii EVs are enriched...

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Bibliographic Details
Published in:Nature Communications
Main Authors: Diana P. Baquero, Guillaume Borrel, Anastasia Gazi, Camille Martin-Gallausiaux, Virginija Cvirkaite-Krupovic, Pierre-Henri Commere, Nika Pende, Stéphane Tachon, Anna Sartori-Rupp, Thibaut Douché, Mariette Matondo, Simonetta Gribaldo, Mart Krupovic
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Online Access:https://doi.org/10.1038/s41467-025-60272-9
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Summary:Abstract Extracellular vesicles (EVs) play many important roles in cells from all domains of life. Here, we characterize EVs produced by Methanobrevibacter smithii, the dominant methanogenic archaeon in the human gut, which contains a peptidoglycan cell wall. We show that M. smithii EVs are enriched in histones and diverse DNA repair proteins. Consistently, the EVs carry DNA and are strongly enriched in extrachromosomal circular DNA (eccDNA) molecules, which originate from excision of a 2.9-kb chromosomal fragment, and a proviral genome. The eccDNA encodes enzymes implicated in biosynthesis of cofactor F420 and coenzyme M, two elements critical for methanogenesis. Furthermore, several of the most abundant EV proteins are implicated in methanogenesis. Cryo-electron tomography suggests that EVs are formed by budding from the cell membrane and are trapped under the peptidoglycan layer prior to liberation through disruptions in the cell wall. Our results reveal parallels with EV biogenesis in bacteria and suggest that M. smithii EVs have potential impact on methane production in the gut.
ISSN:2041-1723