Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites
Abstract The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promotin...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40872-z |
| _version_ | 1797558764348375040 |
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| author | Alexander Y. G. Yip Olivia G. King Oleksii Omelchenko Sanjana Kurkimat Victoria Horrocks Phoebe Mostyn Nathan Danckert Rohma Ghani Giovanni Satta Elita Jauneikaite Frances J. Davies Thomas B. Clarke Benjamin H. Mullish Julian R. Marchesi Julie A. K. McDonald |
| author_facet | Alexander Y. G. Yip Olivia G. King Oleksii Omelchenko Sanjana Kurkimat Victoria Horrocks Phoebe Mostyn Nathan Danckert Rohma Ghani Giovanni Satta Elita Jauneikaite Frances J. Davies Thomas B. Clarke Benjamin H. Mullish Julian R. Marchesi Julie A. K. McDonald |
| author_sort | Alexander Y. G. Yip |
| collection | DOAJ |
| description | Abstract The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites. |
| first_indexed | 2024-03-10T17:35:03Z |
| format | Article |
| id | doaj.art-dfbcc9d5a51c4088979906aa338bfd0e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:35:03Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-dfbcc9d5a51c4088979906aa338bfd0e2023-11-20T09:53:37ZengNature PortfolioNature Communications2041-17232023-08-0114112010.1038/s41467-023-40872-zAntibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolitesAlexander Y. G. Yip0Olivia G. King1Oleksii Omelchenko2Sanjana Kurkimat3Victoria Horrocks4Phoebe Mostyn5Nathan Danckert6Rohma Ghani7Giovanni Satta8Elita Jauneikaite9Frances J. Davies10Thomas B. Clarke11Benjamin H. Mullish12Julian R. Marchesi13Julie A. K. McDonald14Centre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College LondonCentre for Bacterial Resistance Biology, Department of Infectious Disease, Imperial College LondonCentre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College LondonCentre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College LondonCentre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College LondonCentre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College LondonDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary’s Hospital Campus, Imperial College LondonDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary’s Hospital Campus, Imperial College LondonUCL Centre for Clinical Microbiology, University College LondonNIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College Healthcare NHS TrustCentre for Bacterial Resistance Biology, Department of Infectious Disease, Imperial College LondonDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary’s Hospital Campus, Imperial College LondonDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary’s Hospital Campus, Imperial College LondonCentre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College LondonAbstract The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.https://doi.org/10.1038/s41467-023-40872-z |
| spellingShingle | Alexander Y. G. Yip Olivia G. King Oleksii Omelchenko Sanjana Kurkimat Victoria Horrocks Phoebe Mostyn Nathan Danckert Rohma Ghani Giovanni Satta Elita Jauneikaite Frances J. Davies Thomas B. Clarke Benjamin H. Mullish Julian R. Marchesi Julie A. K. McDonald Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites Nature Communications |
| title | Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites |
| title_full | Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites |
| title_fullStr | Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites |
| title_full_unstemmed | Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites |
| title_short | Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites |
| title_sort | antibiotics promote intestinal growth of carbapenem resistant enterobacteriaceae by enriching nutrients and depleting microbial metabolites |
| url | https://doi.org/10.1038/s41467-023-40872-z |
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