Screening anti-viral compounds against a diverse set of Bacteriophages

Under the constant threat of predation by bacteriophages (or phages), bacteria evolved a huge arsenal of anti-phage defense mechanism. The majority of antiphage defense systems reported so far revolve around proteins or RNA complexes that function at the cellular level. Recently, the DNA-intercalating anthracyclines¹ as well as several aminoglycoside antibiotics², produced by Streptomyces, were shown to specifically block DNA replication of various dsDNA phages. Despite this discovery, the precise mechanism by which these compounds exert their effects and the specific phage characteristics that render them susceptible to these substances remain unknown.

Most antiphage molecules reported so far are produced by environmental bacteria of the genus Streptomyces. This study centers on antiphage compounds produced by Streptomyces and seeks to evaluate the specific phage characteristics that render them susceptible to chemical defense mechanisms^1,2. For this purpose, the BASEL phage collection, comprising 69 diverse Escherichia coli phages, as well as several Streptomyces phages from our own collection were screened to investigate sensitivity determinants on the phage genome towards these anti-viral compounds³. This screening revealed distinct and taxonomically-related clusters of phages which are sensitive to specific compounds and emphasize an important impact of phage epigenomic modifications.

References

1 Aël Hardy, Larissa Kever, and Julia Frunzke* "Antiphage small molecules produced by bacteria – beyond protein-mediated defences" (2022), doi: 10.1016/j.tim.2022.08.001

2 Kever, L. et al. "Aminoglycoside Antibiotics Inhibit Phage Infection by Blocking an Early Step of the Infection Cycle" (2022), doi: 10.1128/mbio.00783-22

3 Maffei, E. et al. "Systematic exploration of Escherichia coli phage-host interactions with the BASEL phage collection" (2021), doi: 10.1371/journal.pbio.3001424