Unravelling the collateral damage of antibiotics on gut bacteria

Lisa Maier (), Camille V. Goemans, Jakob Wirbel, Michael Kuhn, Claudia Eberl, Mihaela Pruteanu, Patrick Müller, Sarela Garcia-Santamarina, Elisabetta Cacace, Boyao Zhang, Cordula Gekeler, Tisya Banerjee, Exene Erin Anderson, Alessio Milanese, Ulrike Löber, Sofia K. Forslund, Kiran Raosaheb Patil, Michael Zimmermann, Bärbel Stecher, Georg Zeller, Peer Bork and Athanasios Typas ()
Additional contact information
Lisa Maier: European Molecular Biology Laboratory
Camille V. Goemans: European Molecular Biology Laboratory
Jakob Wirbel: European Molecular Biology Laboratory
Michael Kuhn: European Molecular Biology Laboratory
Claudia Eberl: LMU Munich
Mihaela Pruteanu: European Molecular Biology Laboratory
Patrick Müller: University of Tübingen
Sarela Garcia-Santamarina: European Molecular Biology Laboratory
Elisabetta Cacace: European Molecular Biology Laboratory
Boyao Zhang: European Molecular Biology Laboratory
Cordula Gekeler: University of Tübingen
Tisya Banerjee: European Molecular Biology Laboratory
Exene Erin Anderson: European Molecular Biology Laboratory
Alessio Milanese: European Molecular Biology Laboratory
Ulrike Löber: Experimental and Clinical Research Center, a cooperation of Charité - Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine
Sofia K. Forslund: European Molecular Biology Laboratory
Kiran Raosaheb Patil: European Molecular Biology Laboratory
Michael Zimmermann: European Molecular Biology Laboratory
Bärbel Stecher: LMU Munich
Georg Zeller: European Molecular Biology Laboratory
Peer Bork: European Molecular Biology Laboratory
Athanasios Typas: European Molecular Biology Laboratory

Nature, 2021, vol. 599, issue 7883, 120-124

Abstract: Abstract Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease1. 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 species2. 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 animal3–5 and human6,7 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.

Date: 2021
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DOI: 10.1038/s41586-021-03986-2

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