Unravelling the collateral damage of antibiotics on gut bacteria

Tools

Item Type:	Article
Title:	Unravelling the collateral damage of antibiotics on gut bacteria
Creators Name:	Maier, L., Goemans, C.V., Wirbel, J., Kuhn, M., Eberl, C., Pruteanu, M., Müller, P., Garcia-Santamarina, S., Cacace, E., Zhang, B., Gekeler, C., Banerjee, T., Anderson, E.E., Milanese, A., Löber, U., Forslund, S.K., Patil, K.R., Zimmermann, M., Stecher, B., Zeller, G., Bork, P. and Typas, A.
Abstract:	Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species. Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for β-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal and human gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota.
Keywords:	Anaerobic Bacteria, Anti-Bacterial Agents, Bacteria, Bacteroides, Clostridioides difficile, Dicumarol, Erythromycin, Feces, Gastrointestinal Microbiome, Germ-Free Life, Macrolides, Microbiota, Symbiosis, Tetracyclines, Animals, Mice
Source:	Nature
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Volume:	599
Page Range:	120-124
Date:	4 November 2021
Additional Information:	Copyright © The Author(s), under exclusive licence to Springer Nature Limited 2021
Official Publication:	https://doi.org/10.1038/s41586-021-03986-2
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

Repository Staff Only: item control page