Understanding phage Receptor-binding protein interaction with host surface receptor: the key for phage-Mediated detection and elimination of Pseudomonas aeruginosa.

Pseudomonas aeruginosa poses a significant clinical challenge due to its intrinsic and acquired antimicrobial resistance and robust biofilm formation, which complicates treatment. Bacteriophages (phages), viruses targeting bacteria, are emerging as a promising alternative or adjunct to combat multidrug-resistant P. aeruginosa infections. This review systematically examines the taxonomic diversity of phages infecting P. aeruginosa, with emphasis on those that remain unclassified at the family taxonomic level, such as Pbunavirus and Pakpunavirus. It comprehensively synthesizes current knowledge on phage receptor-binding proteins (RBPs) - the molecular determinants of host specificity - and their corresponding receptors on the P. aeruginosa surface, such as lipopolysaccharide (LPS), pili, flagella, outer membrane proteins, and alginate. Critically, the review underscores the urgent need to decipher the precise molecular mechanisms governing RBP-receptor interactions. A deeper understanding of these specific recognition events is paramount. This knowledge is essential not only for rationally optimizing phage therapy efficacy, including through engineered phages or RBP-based antimicrobials, but also for developing highly sensitive and specific phage-derived diagnostic tools, utilizing whole phages or purified RBPs as recognition elements for rapid P. aeruginosa detection.