Journal Article

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

Satta, Giovanni, Mostyn, Phoebe, King, Olivia G., Horrocks, Victoria, Kurkimat, Sanjana, Mullish, Benjamin H., Davies, Frances J., Clarke, Thomas B., Yip, Alexander Y. G., Omelchenko, Oleksii, Jauneikaite, Elita, Marchesi, Julian R., McDonald, Julie A. K., Ghani, Rohma, Danckert, Nathan

2023

Overview

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. Broad-spectrum antibiotics can kill harmless bacteria in our intestine, thus facilitating invasion by antibiotic-resistant bacteria such as carbapenem-resistant Enterobacteriaceae (CRE). Here, Yip et al. show that killing gut bacteria with antibiotics leads to enrichment of nutrients and depletion of inhibitory microbial metabolites, which overall potentiates CRE growth.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 140/131 / 45/22 / 45/23 / 631/326/22/1434 / 631/326/2565/2134 / 631/326/41/1969 / 631/326/421 / 64/60 / Actinobacteria / Animals / Anti-Bacterial Agents - pharmacology / Antibiotic resistance / Antibiotics / Bacteria / Bacteroidetes / Carbapenem-Resistant Enterobacteriaceae / Carbon sources / Colonization / Commensals / CRE bacteria / Depletion / Digestive system / E coli / Enrichment / Enterobacteriaceae / Escherichia coli / Gastrointestinal tract / Humanities and Social Sciences / Humans / Intestinal microflora / Intestinal Neoplasms / Intestine / Metabolites / Mice / Microbiota / Microorganisms / multidisciplinary / Nitrogen sources / Nutrients / Science / Science (multidisciplinary)