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Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites

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 and Julie A. K. McDonald ()
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Alexander Y. G. Yip: Imperial College London
Olivia G. King: Imperial College London
Oleksii Omelchenko: Imperial College London
Sanjana Kurkimat: Imperial College London
Victoria Horrocks: Imperial College London
Phoebe Mostyn: Imperial College London
Nathan Danckert: Imperial College London
Rohma Ghani: Imperial College London
Giovanni Satta: University College London
Elita Jauneikaite: Imperial College London
Frances J. Davies: Imperial College Healthcare NHS Trust
Thomas B. Clarke: Imperial College London
Benjamin H. Mullish: Imperial College London
Julian R. Marchesi: Imperial College London
Julie A. K. McDonald: Imperial College London

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40872-z

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