Revisiting lactococcal abortive infection-like antiphage systems: diversity, structures, and mechanisms.

Lactococcus lactis and Lactococcus cremoris are cornerstone bacterial species employed in the production of fermented dairy products such as cheese. However, the non-sterile dairy processing environment regularly exposes these lactococci to phage infection. To counteract this phage threat, bacteria have evolved a wide range of defence mechanisms, including so-called abortive infection Abi(-like) systems, of which many (AbiA to AbiZ) were originally discovered in Lactococcus. Recent discoveries have expanded the list of Abi-like systems in Lactococcus species. In this review, we focus on systems historically, phenotypically, or mechanistically classified as Abi, critically examine and revisit their antiphage activity spectrum and interference with the phage lytic cycle, as well as mechanistic insights of lactococcal Abi-like systems as obtained through the study of phage escape mutants. Furthermore, we group various Abi-like systems based on structural superimposition and use predicted domain information to explore or expand on their mechanism of action. Finally, we show that despite many Abi-like systems being discovered due to their presence on plasmids, most anti-phage defence systems appear to be chromosomally encoded in sequenced Lactococcus strains. Our findings support the notion that co-evolution of Lactococcus species with their phages, possibly accelerated by the extensive application of these bacteria in dairy fermentations, has resulted in the acquisition of a diverse array of phage defence mechanisms, including Abi-like systems.