Suppression of gut colonization by multidrug-resistant Escherichia coli clinical isolates through cooperative niche exclusion
Human gut colonization by multi-drug resistant Enterobacterales (MDR-E) poses a risk for subsequent infections. Because of the collateral damage antibiotics cause to the microbiota, microbiome-based interventions aimed at promoting decolonization have garnered interest. In this study, we evaluate the strain-specific potential of 430 commensal Escherichia coli isolates to inhibit the growth of an MDR E. coli strain. Comparative analyses using in vitro, ex vivo, and mouse models reveal that only a subset of commensal strains can facilitate gut decolonization. Bioinformatic and experimental analyses of the antagonism among representative strains demonstrate that both direct and indirect carbohydrate competition contribute to niche exclusion between E. coli strains. Finally, the combination of a protective E. coli strain with a Klebsiella oxytoca strain enhances the inhibitory potential against metabolically diverse MDR E. coli strains and additional MDR-E species, highlighting that rationally designed metabolically complementary approaches can contribute to developing next-generation probiotics with broad-spectrum activity.
Authors
- Niels Pfennigwerth (ORCID: https://orcid.org/0000-0002-6403-5646)
- Katharina Schaufler (ORCID: https://orcid.org/0000-0002-2669-8799)
- Till Robin Lesker (ORCID: https://orcid.org/0000-0002-3085-6438)
- Marco Galardini (ORCID: https://orcid.org/0000-0003-2018-8242)
- Agata Bielecka‐Dąbrowa (ORCID: https://orcid.org/0000-0001-6666-3999)
- Till Strowig (ORCID: https://orcid.org/0000-0003-0185-1459)
- Dirk Schlüter (ORCID: https://orcid.org/0000-0003-1478-3328)
- Jennifer Schauer (ORCID: https://orcid.org/0000-0001-5975-0429)
- Marie Wende
- Lisa Osbelt (ORCID: https://orcid.org/0000-0002-4862-650X)
- Bamu F. Damaris (ORCID: https://orcid.org/0000-0003-0465-0425)
- Éva Almási (ORCID: https://orcid.org/0000-0001-5042-5478)
- Katrin Anja Winter
- Sören G. Gatermann (ORCID: https://orcid.org/0000-0002-8662-218X)
- Lea Eisenhard
- Uthayakumar Mutukumarasamy
Institutions
- Universitätsmedizin Greifswald (DE)
- Medizinische Hochschule Hannover (DE)
- German Center for Infection Research (DE)
- Helmholtz Centre for Infection Research (DE)
- Helmholtz Institute for RNA-based Infection Research (DE)
- Centre for Individualised Infection Medicine (DE)
- Center for Experimental and Clinical Infection Research (DE)
- Ruhr University Bochum (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1038/s41467-025-61327-7
- Citations
- 10
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 8.06
Funders
- Joint Programming Initiative on Antimicrobial Resistance
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- European Social Fund