bioRxivMicrobiology
Aminoglycoside antibiotics inhibit phage infection by blocking an early step of the phage infection cycle
L. Kever, A. Hardy, T. Luthe, M. Huennefeld, C. Gaetgens, L. Milke, J. Wiechert, J. Wittmann, C. Moraru, J. Marienhagen, J. Frunzke
Abstract
In response to viral predation, bacteria have evolved a wide range of defense mechanisms, which rely mostly on proteins acting at the cellular level. Here, we show that aminoglycosides, a well-known class of antibiotics produced by Streptomyces, are potent inhibitors of phage infection in widely divergent bacterial hosts. We demonstrate that aminoglycosides block an early step of the viral life cycle, prior to genome replication. Phage inhibition was also achieved using supernatants from natural aminoglycoside producers, hinting at a broad physiological significance of the antiviral properties of aminoglycosides. Strikingly, we show that acetylation of the aminoglycoside antibiotic apramycin abolishes its antibacterial effect, but retains its antiviral properties. Altogether, this study expands the knowledge of potential aminoglycoside functions in bacterial communities suggesting that aminoglycosides are not only used by their producers as toxic molecules against their bacterial competitors, but could also provide protection against the threat of phage predation at the community level.
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Decoupling the molecular versatility of aminoglycosides via drug or target modification enables community-wide antiphage defense
L. Kever, Q. Zhang, … J. Frunzke·bioRxiv·Feb 27, 2024
- Aminoglycoside antibiotics inhibit mycobacteriophage infection
Z. Jiang, J. Wei, … Y. Li·AntibioticsPeer-reviewed·Oct 19, 2020
- In vitro analysis of colistin and ciprofloxacin antagonism of Pseudomonas aeruginosa phage PEV2 infection activities
K. M. Danis-Wlodarczyk, A. Cai, … S. T. Abedon·bioRxiv·Dec 2, 2020
- Antibiotics that affect translation can antagonize phage infectivity by interfering with the deployment of counter-defences.
B. J. Pons, T. Dimitriu, … S. van Houte·bioRxiv·Sep 7, 2022
- Phage-Antibiotic Synergy Is Driven By A Unique Combination Of Antibacterial Mechanism Of Action And Stoichiometry
C. Gu Liu, S. I. Green, … A. W. Maresso·mBioPeer-reviewed·Aug 25, 2020
- Temperate phage-antibiotic synergy is widespread, but varies by phage, host, and antibiotic pairing
Rabia Fatima, Alexander P. Hynes·mBioPeer-reviewed·Dec 20, 2024