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Unni, R.* ; Andreani, N.A.* ; Vallier, M.* ; Heinzmann, S.S. ; Taubenheim, J.* ; Guggeis, M.A.* ; Tran, F.* ; Vogler, O.* ; Künzel, S.* ; Hövener, J.B.* ; Rosenstiel, P.* ; Kaleta, C.* ; Dempfle, A.* ; Unterweger, D.* ; Baines, J.F.*

Evolution of E. coli in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance.

Gut Microbes 15:2286675 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Inflammatory bowel disease (IBD) is a persistent inflammatory condition that affects the gastrointestinal tract and presents significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has rarely been studied from an evolutionary perspective. In this study, we aimed to investigate the evolution of resident bacteria during intestinal inflammation and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance. Here, we perform an in vivo evolution experiment of E. coli in a gnotobiotic mouse model of IBD, followed by multiomic analyses to identify disease-specific genetic and phenotypic changes in bacteria that evolved in an inflamed versus a non-inflamed control environment. Our results demonstrate distinct evolutionary changes in E. coli specific to inflammation, including a single nucleotide variant that independently reached high frequency in all inflamed mice. Using ex vivo fitness assays, we find that these changes are associated with a higher fitness in an inflamed environment compared to isolates derived from non-inflamed mice. Further, using large-scale phenotypic assays, we show that bacterial adaptation to inflammation results in clinically relevant phenotypes, which intriguingly include collateral sensitivity to antibiotics. Bacterial evolution in an inflamed gut yields specific genetic and phenotypic signatures. These results may serve as a basis for developing novel evolution-informed treatment approaches for patients with intestinal inflammation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter E. Coli ; Inflammatory Bowel Disease ; Evolutionary Trade-offs ; Experimental Evolution; Adaptive Evolution; Commensal Bacteria; Escherichia-coli; Crohns-disease; Fusidic Acid; Identification; Expression; Reduction; Regulator; Dynamics
ISSN (print) / ISBN 1949-0976
e-ISSN 1949-0984
Zeitschrift Gut Microbes
Quellenangaben Band: 15, Heft: 2, Seiten: , Artikelnummer: 2286675 Supplement: ,
Verlag Landes Bioscience
Verlagsort 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical BioGeoChemistry (BGC)
Förderungen German Federal Ministry for Education and Research
International Max -Planck Research School for Evolutionary Biology (IMPRS EvolBio)
Deutsche Forschungsgemeinschaft (DFG) Research Unit