Abstract
R-pyocins are phage tail-like protein complexes produced by Pseudomonas aeruginosa that deliver a single, lethal hit by depolarizing the target cell membrane. Unlike phages, R-pyocins lack capsids and DNA, and their killing is highly specific, being determined by tail fibre proteins that recognize subtype-specific LPS receptors on susceptible strains. Five known subtypes (R1-R5) vary in host range, with R5 displaying the broadest activity. R-pyocin expression is tightly regulated by the SOS response, linking their release to environmental stress. Their non-replicative mechanism and metabolic independence make them especially promising for targeting multidrug-resistant and biofilm-associated P. aeruginosa infections, such as those seen in cystic fibrosis and chronic wounds. Preclinical studies support their therapeutic potential, and bioengineering approaches have extended their target range. With their high specificity, rapid action and adaptability, R-pyocins are strong candidates for next-generation precision antimicrobials.