Baquero Diana P, Borrel Guillaume, Gazi Anastasia, Martin-Gallausiaux Camille, Cvirkaite-Krupovic Virginija, Commere Pierre-Henri, Pende Nika, Tachon Stéphane, Sartori-Rupp Anna, Douché Thibaut, Matondo Mariette, Gribaldo Simonetta, Krupovic Mart
Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit, Paris, France.
Institut Pasteur, Université Paris Cité, Evolutionary Biology of the Microbial Cell, Paris, France.
Nat Commun. 2025 Jun 3;16(1):5093. doi: 10.1038/s41467-025-60272-9.
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 F 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.
细胞外囊泡（EVs）在生命各领域的细胞中发挥着许多重要作用。在此，我们对由史密斯甲烷短杆菌产生的细胞外囊泡进行了表征，该菌是人类肠道中占主导地位的产甲烷古菌，其含有肽聚糖细胞壁。我们发现史密斯甲烷短杆菌的细胞外囊泡富含组蛋白和多种DNA修复蛋白。一致的是，这些细胞外囊泡携带DNA，并且在染色体外环状DNA（eccDNA）分子中高度富集，这些分子源自一个2.9 kb染色体片段的切除以及一个前病毒基因组。该eccDNA编码参与辅因子F和辅酶M生物合成的酶，这两种元素对产甲烷作用至关重要。此外，几种含量最丰富的细胞外囊泡蛋白也与产甲烷作用有关。冷冻电子断层扫描表明，细胞外囊泡是通过从细胞膜出芽形成的，并在通过细胞壁破裂释放之前被困在肽聚糖层下。我们的结果揭示了与细菌中细胞外囊泡生物发生的相似之处，并表明史密斯甲烷短杆菌的细胞外囊泡可能对肠道中的甲烷产生有潜在影响。
