Phage–host interactions are defined by the molecular specificity of receptor-binding proteins (RBPs), which determine the efficacy of infection and the host range. The genetic and structural variability of bacterial receptor molecules is essential for designing effective phage therapeutics and mitigating resistance. This study investigated four receptor-binding proteins, tarS , tarL , tagO , and tagG , in multiple Staphylococcus aureus isolates. Single-nucleotide polymorphism (SNP) analysis was performed to assess receptor diversity and evolutionary conservation. Molecular docking was conducted between these bacterial receptors and Staphylococcus phage tail and spike proteins (TPCARΦ38, TPCARΦ53, TSCARΦ53, and SPCARΦ58) to evaluate binding affinity and interaction specificity. SNP profiling revealed conserved and strain-specific mutations across the receptor genes, predominantly transition-type substitutions, without insertions or deletions. Docking simulations demonstrated strong receptor–phage interactions, with binding energies ranging from 8 to 14 kcal/mol. Despite underlying genetic variation, conserved docking hotspots suggested functional stability and evolutionary pressure to preserve key receptor-binding motifs essential for phage attachment. The findings indicate a coevolutionary balance between S. aureus receptor polymorphism and phage adaptation. Such receptor diversity may drive partial resistance while maintaining susceptibility to related phages. This molecular understanding of RBP evolution provides valuable insights for designing rational, broad-spectrum, or combination phage therapy strategies against S. aureus infections.
Vinodkumar et al. (Thu,) studied this question.