
Bacterial extracellular matrix (a loose network of polymers), such as slime layers (e.g., Campylobacter fetus slime layer) or capsules (e.g., Escherichia coli K1 capsule, and Klebsiella pneumoniae capsule) can cover the bacterial surface and makes the phage receptors inaccessible for phage binding so that protecting bacteria from phage attack. Bacteria have generated several barriers to prevent phage attachment to their cell surface, such as hidden receptors with extracellular matrix. Several bacterial cell surface proteins, lipopolysaccharides, and other surface polysaccharide and carbohydrate moieties can serve as receptors for phages. Phage adsorption to the bacterial cell surface is performed through specific receptors as the first step of phage infection cycle. These host-phage interaction is a complex and multifaceted process, which influences the diversity of genetic makeup of both bacteria and their predators, and it is one of the driving forces creating genetically fit populations from both sides. On the contrary, phages developed several counterstrategies and circumvent the phage resistance warfare. Bacteria can evade the phage attack via several mechanisms and some of these strategies include the following: DNA restriction-modification (R-M), spontaneous mutations, blocking of phage receptors, production of competitive inhibitors, and extracellular matrix and acquired immunity via the clustered regularly interspaced short palindromic repeats and associated proteins (CRISPR-Cas) mechanism. Phages, by developing resistance, play a crucial role in controlling bacterial populations in most, if not in all, the milieus. It is part of continuous cycles of coexistence and evolution, resulting in phage-resistant hosts protecting bacterial lineages, while counter-resistant phages threaten such strains. 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.īacteria and phages are seemingly involved in a continuous battle. 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. On the contrary, phages develop anti-phage resistance defense mechanisms in consortium with each of these bacterial phage resistance strategies with small fitness cost. 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. These defense mechanisms are mainly related to either the host or phage-derived proteins and other associated structures and biomolecules. Most studied antiphage systems are associated with phages, whose genomic matter is double-stranded-DNA.

Several studies indicated that the bacterial immune arsenal towards phage is quite diverse and uses different components of the host machinery. Bacteria and their predators, bacteriophages, or phages are continuously engaged in an arms race for their survival using various defense strategies.
