Revenge of the phages: defeating bacterial defences

Phages and bacteria are seemingly engaged in an endless battle. In the presence of bacterial antiviral barriers, phages rely on several diverse counter-strategies to usurp their hosts and ensure phage propagation.Phages can readily modify their receptor-binding protein to adsorb to evolving bacterial populations. Phages can also use strategies such as diversity-generating retroelements to facilitate the recognition of multiple bacterial receptors. Moreover, if host receptors are masked by capsular polysaccharides, some phages possess degrading enzymes to hydrolyse this material and access the receptor.When the phage genome enters its bacterial host, it can be targeted by various nucleic acid cleavage enzymes such as restriction–modification and CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) systems. To protect against these systems, phages use an array of strategies, including anti-restriction–modification and anti-CRISPR systems, and point mutations in specific sequences.Abortive-infection mechanisms lead to the altruistic death of a phage-infected cell (for example, through induction of a toxin), thereby limiting phage propagation. Phages circumvent this hurdle mainly by mutating specific genes or through the production or hijacking of antitoxins that neutralize the bacterial toxin.This is a rapidly expanding field of research, but many antiphage systems and many strategies used to escape these bacterial defences remain to be discovered. A better understanding of phage–host interactions is also needed to minimize the negative impact of phages on food production and biotechnology applications, as well as to maximize the use of phages as antibacterial agents.