Coordinated host resistance and distinct phage strategies shape biofilm-phage dynamics in Pseudomonas aeruginosa

Temperate and virulent phages coexist in natural environments and can collaboratively contribute to the lysis of bacterial biofilms. However, their therapeutic potential and the dynamics of phage-biofilm interactions, particularly in clinical contexts, remain poorly understood. In this study, we demonstrated the strong biofilm-lysing capabilities of the temperate phage PaoP1 and virulent phage PaoP5 against Pseudomonas aeruginosa biofilms, highlighting their potential for phage therapy. RNA-seq analysis revealed a shared host resistance mechanism involving the downregulation of flagellar biosynthesis and enhanced biofilm formation. Despite this common host response, the two phages exhibited distinct infection strategies: PaoP1 integrated quiescently into the host genome, while PaoP5 rapidly and abundantly expressed its genes, potentially hijacking the host transcriptional machinery through an as-yet-unknown mechanism. These findings deepen our understanding of phage-biofilm interactions and support the development of phage-based approaches to treat biofilm-associated infections.