<i>Pseudomonas aeruginosa</i> DEV phage exploits the essential LptD outer membrane protein as receptor for adsorption

<i>Pseudomonas aeruginosa</i> phage DEV uses the O-antigen of lipopolysaccharide as its primary receptor. In this study, we found that LptD, an essential and highly conserved outer membrane protein, serves as the secondary receptor for DEV. This interaction is mediated by a specialized receptor-binding fiber composed of the DEV proteins <i>gp54</i>, <i>gp55</i>, and <i>gp56</i>. We posit that the <i>gp56-gp55-gp54</i> genes form a functional module, possibly disseminated via horizontal gene transfer among distantly related phages, involved in tail sealing and the regulated unplugging of the tail upon interaction with the bacterial receptor. Given the high conservation of receptor-binding proteins among phages in the DEV <i>Litunavirus</i> genus, we anticipate that other members of this genus may also use LptD as their receptor. Since <i>Litunaviruses</i> are actively explored for phage therapy, insights into the interaction between DEV and its receptors could help develop more effective and targeted phage-based treatments.