Within-host evolution of a gut pathobiont facilitates liver translocation.

Autor: Yang Y; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Nguyen M; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Khetrapal V; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Sonnert ND; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA., Martin AL; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Chen H; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Kriegel MA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.; Department of Translational Rheumatology and Immunology, Institute of Musculoskeletal Medicine, University of Münster, Münster, Germany.; Section of Rheumatology and Clinical Immunology, Department of Medicine, University Hospital Münster, Münster, Germany., Palm NW; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. noah.palm@yale.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Jul; Vol. 607 (7919), pp. 563-570. Date of Electronic Publication: 2022 Jul 13.
DOI: 10.1038/s41586-022-04949-x
Abstrakt: Gut commensal bacteria with the ability to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases 1-4 . However, the key factors that dictate bacterial translocation remain unclear. Recent studies have revealed that gut microbiota strains can adapt and evolve throughout the lifetime of the host 5-9 , raising the possibility that changes in individual commensal bacteria themselves over time may affect their propensity to elicit inflammatory disease. Here we show that within-host evolution of the model gut pathobiont Enterococcus gallinarum facilitates bacterial translocation and initiation of inflammation. Using a combination of in vivo experimental evolution and comparative genomics, we found that E. gallinarum diverges into independent lineages adapted to colonize either luminal or mucosal niches in the gut. Compared with ancestral and luminal E. gallinarum, mucosally adapted strains evade detection and clearance by the immune system, exhibit increased translocation to and survival within the mesenteric lymph nodes and liver, and induce increased intestinal and hepatic inflammation. Mechanistically, these changes in bacterial behaviour are associated with non-synonymous mutations or insertion-deletions in defined regulatory genes in E. gallinarum, altered microbial gene expression programs and remodelled cell wall structures. Lactobacillus reuteri also exhibited broadly similar patterns of divergent evolution and enhanced immune evasion in a monocolonization-based model of within-host evolution. Overall, these studies define within-host evolution as a critical regulator of commensal pathogenicity that provides a unique source of stochasticity in the development and progression of microbiota-driven disease.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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