Bacteriophage-Host Dynamics: Structural Basis, Receptor Interactions, and the Evolutionary Arms Race

Bacteriophages, the most abundant biological entities on Earth, play a central role in regulating microbial populations and driving bacterial evolution. Dominated by tailed double-stranded DNA viruses (Caudovirales), phages orchestrate complex interactions with their hosts that begin with the highly specific process of adsorption, mediated by receptor-binding proteins and host surface-localized receptors. This review delves into the molecular architecture and specificity of phage-host recognition, emphasizing the diverse range of bacterial receptors- including lipopolysaccharides, outer membrane proteins, teichoic acids, pili, flagella, and capsular polysaccharides- found in both Gram-negative and Gram-positive bacteria. In parallel, we explore the multi-layered defense mechanisms employed by bacteria to evade infection, including receptor masking, biofilm-mediated resistance, superinfection exclusion, toxin-antitoxin systems, CRISPR-Cas immunity, and restriction-modification systems. In response, phages have evolved counterstrategies including structural alterations in receptor-binding proteins, anti-CRISPR factors, DNA mimicry, and dual adsorption modules to overcome host immunity. The review integrates recent advances in our understanding of phage-host molecular conflicts, drawing attention to the evolutionary dynamics shaping phage-host coadaptation and highlighting the translational potential of phage biology in therapeutic and biotechnological applications.