Toothpicks, logic, and next-generation sequencing: systematic investigation of bacteriophage-host interactions.

Bacteriophages are abundant and diverse predators that drive community dynamics in many ecosystems and hold great potential for biotechnology and as therapeutics for bacterial infections. Previous research has largely explored phage-host interactions one-by-one, which limited our ability to observe phenotypic patterns, to uncover their genetic basis, and to unravel the underlying molecular mechanisms. However, the famous 'toothpicks and logic' were recently joined by large-scale sequencing of phage genomes and bacterial genome-wide screens that enable us to systematically investigate phage-host interactions.

Antiviral death punch by ADP-ribosylating bacterial toxins.

Toxin-antitoxin systems can defend bacteria against phages by shutting down infected cells, but the links between their molecular mechanisms and biological functions have remained underexplored. LeRoux et al. now show how the DNA-targeting ADP-ribosylation activity of DarTG impairs phage replication but is overcome by dedicated viral inhibitors and evolved tolerance.

Systematic exploration of Escherichia coli phage-host interactions with the BASEL phage collection.

Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of the molecular mechanisms underlying phage-host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically.