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)
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
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2023
Prepublished im Jahr
0
HGF-Berichtsjahr
2023
ISSN (print) / ISBN
1949-0976
e-ISSN
1949-0984
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 15,
Heft: 2,
Seiten: ,
Artikelnummer: 2286675
Supplement: ,
Reihe
Verlag
Landes Bioscience
Verlagsort
530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
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Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Environmental Sciences
PSP-Element(e)
G-504800-001
Förderungen
German Federal Ministry for Education and Research
International Max -Planck Research School for Evolutionary Biology (IMPRS EvolBio)
Deutsche Forschungsgemeinschaft (DFG) Research Unit
Copyright
Erfassungsdatum
2023-12-20