Aminoglycoside antibiotics inhibit phage infection by blocking an early step of the phage infection cycle

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.

The bacterial toxin colibactin triggers prophage induction

“…More generally, the modulation of phage behaviours represents a distinct and underappreciated ecological role for microbial natural products. Our findings add to this growing understanding 14,[40][41][42][43] and, notably, demonstrate phage induction by a natural product in co-culture. Finally, as links between the human gut virome and diseases continue to be established 44 , our findings set the stage for further investigations of how gut bacterial metabolite production modulates phage behaviours and may influence human disease.…”

An expanding arsenal of immune systems that protect bacteria from phages

“…Systematic analyses of defense islands in tens of thousands of microbial genomes (Doron et al, 2018; Gao et al, 2020; Rousset et al, 2022) have led to the discovery of several dozens of new defense systems exhibiting a variety of defensive mechanisms. These include systems that utilize second messenger signaling to mediate defense (Cohen et al, 2019; Ofir et al, 2021; Tal et al, 2021a; Whiteley et al, 2019), systems that produce antiviral molecules (Bernheim et al, 2021; Kever et al, 2021; Kronheim et al, 2018), and systems that rely on reverse transcription of small RNAs as part of the defensive machinery (Gao et al, 2020; Millman et al, 2020a).…”

Discovery of phage determinants that confer sensitivity to bacterial immune systems

“…However, studies over the past few years have revealed a plethora of additional defense mechanisms commonly employed by bacteria. These include phage restriction by prokaryotic Argonaute proteins (Garb et al, 2021;Koopal et al, 2022;Kuzmenko et al, 2020;Zaremba et al, 2021), production of small molecules that block phage propagation (Bernheim et al, 2021;Kever et al, 2022;Kronheim et al, 2018), depletion of molecules essential for phage replication (Garb et al, 2021;Hsueh et al, 2022;Ofir et al, 2021;Tal et al, 2022), systems that use small molecule signaling to activate immune effectors (Cohen et al, 2019;Tal et al, 2021;Whiteley et al, 2019), retrons that involve reverse transcription of non-coding RNAs (Bobonis et al, 2022;Gao et al, 2020;Millman et al, 2020), and more (Doron et al, 2018;Gao et al, 2020;Goldfarb et al, 2015;Johnson et al, 2022;Millman et al, 2022;Ofir et al, 2018;Rousset et al, 2022;Vassallo et al, 2022).…”