PuSH - Publication Server of Helmholtz Zentrum München

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)
Publ. Version/Full Text 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.
Impact Factor
Scopus SNIP
Altmetric
12.200
0.000
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords 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
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1949-0976
e-ISSN 1949-0984
Journal Gut Microbes
Quellenangaben Volume: 15, Issue: 2, Pages: , Article Number: 2286675 Supplement: ,
Publisher Landes Bioscience
Publishing Place 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
Reviewing status Peer reviewed
POF-Topic(s) 30202 - Environmental Health
Research field(s) Environmental Sciences
PSP Element(s) G-504800-001
Grants German Federal Ministry for Education and Research
International Max -Planck Research School for Evolutionary Biology (IMPRS EvolBio)
Deutsche Forschungsgemeinschaft (DFG) Research Unit
PubMed ID 38059748
Erfassungsdatum 2023-12-20