The Battle between Bacteria and Bacteriophages: A Conundrum to Their Immune System.

Bacteria and their predators, bacteriophages, or phages are continuously engaged in an arms race for their survival using various defense strategies. Several studies indicated that the bacterial immune arsenal towards phage is quite diverse and uses different components of the host machinery. Most studied antiphage systems are associated with phages, whose genomic matter is double-stranded-DNA. These defense mechanisms are mainly related to either the host or phage-derived proteins and other associated structures and biomolecules. Some of these strategies include DNA restriction-modification (R-M), spontaneous mutations, blocking of phage receptors, production of competitive inhibitors and extracellular matrix which prevent the entry of phage DNA into the host cytoplasm, assembly interference, abortive infection, toxin-antitoxin systems, bacterial retrons, and secondary metabolite-based replication interference. On the contrary, phages develop anti-phage resistance defense mechanisms in consortium with each of these bacterial phage resistance strategies with small fitness cost. These mechanisms allow phages to undergo their replication safely inside their bacterial host's cytoplasm and be able to produce viable, competent, and immunologically endured progeny virions for the next generation. In this review, we highlight the major bacterial defense systems developed against their predators and some of the phage counterstrategies and suggest potential research directions.