Conserved domains can be found across distinct phage defence systems

Abstract

Bacteria are continuously exposed to predation from bacteriophages (phages) and, in response, have evolved a broad range of defence systems. These systems can prevent the replication of phages and other mobile genetic elements (MGE). Defence systems are often encoded together in genomic loci defined as “defence islands”, a tendency that has been extensively exploited to identify novel antiphage systems. In the last few years, >100 new antiphage systems have been discovered, and some display homology to components of the immune systems of plants and animals. In many instances, prediction tools have found domains with similar predicted functions present as different combinations within distinct antiphage systems. In this Perspective Article, we review recent reports describing the discovery and the predicted domain composition of several novel antiphage systems. We discuss several examples of similar protein domains adopted by different antiphage systems, including domains of unknown function (DUFs), domains involved in nucleic acid recognition and degradation, and domains involved in NAD+ depletion. We further discuss the potential evolutionary advantages that could have driven the independent acquisition of these domains by different antiphage systems.

The structural basis of hyperpromiscuity in a core combinatorial network of Type II toxin-antitoxin and related phage defence systems

“…This supports previous observations that toxins and antitoxins that are diverse at the sequence level can have the same structural fold [60]. A similar conservation of domains is also seen in phage defence systems [61].…”

Multi-conflict islands are a widespread trend withinSerratiaspp

“…Our investigation of the LptG-YjiA islands’ cargo further led to the intriguing revelation that the anti-phage system SDIC4, found in two different subtypes, co-opted the same fold as a poorly-characterised predicted T6SS-related protein for phage defence (Figure 4-5). This discovery aligns with a growing body of reports documenting domains of diverse origins, including housekeeping proteins, being co-opted for defence against phages 3,4,13,36,50 . Furthermore, it corresponds to observed overlaps between toxin-antitoxin systems and anti-phage defence mechanisms 36,51–53 .…”

“…The increasing number of discovered and characterized anti-phage systems reveals a conserved tendency of shared defence domains 13 . These domains can be assembled in various configurations, contributing to a broad and diverse defence arsenal.…”

“…Interestingly, a considerable number of newly-discovered anti-phage systems show homology and resemblance to components of the innate immunity pathways of eukaryotes [6][7][8][9][10][11] . For example, several anti-phage systems harbour a Toll/IL-1 receptor (TIR) domain 4,5,12,13 . In the Thoeris system this domain is used for the production of the isomer of cyclic adenosine 5'-diphosphate-ribose (cADPR) signalling molecule whereas in other instances TIR domains can harbour NADase activity that leads to impaired survival of phage-infected cells 1,4,12,14 .…”

Synergistic anti-phage activity of bacterial defence systems

“…These synergistic interactions and co-opting mechanisms likely play an important role in the evolution of defence systems and the emergence of multiple defence system variants, as observed for CRISPR-Cas 82 , CBASS 19 , Lamassu 6 , Shield 83 , and others. The modularity of anti-phage immunity is further evident in sharing of proteins and functional domains across distinct defence systems 84 , such as HNH-endonuclease in Septu, Zorya II and type II CRISPR-Cas 2 , NucC in CBASS III 85 and CRISPR-Cas type III 86 , TOPRIM domain in Gabija 3 , Wadjet 2 , and PARIS 4 , and P-loop NTPases, including helicases, in a broad diversity of defence systems including CRISPR-Cas type I, Gabija, PrrC, tmn and many others 2,3,75 . Expanding our understanding of the mechanisms underlying the modularity of defence systems is expected to provide insights into their adaptive potential and evolutionary dynamics in the perennial arms race between bacteria and phages.…”