Isolation and characterization of a novel K3-type capsule-targeting phage for the treatment of carbapenem-resistant <i>Acinetobacter baumannii</i>

The global spread of MDR-AB, particularly carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) strains with various capsule types, necessitates the development of innovative antimicrobial strategies. In this study, we identify phage P11B as a potent lytic agent against KL3 CRAB and reveal an evolutionary trade-off: mutations in capsule biosynthesis genes (<i>pgi</i>, <i>algC</i>, <i>galU</i>) that confer phage resistance also directly reduce virulence. This biological constraint addresses a significant limitation of phage therapy by ensuring that resistant mutants remain less pathogenic. Our findings mechanistically link modifications in phage receptors to a reduction in virulence, thereby advancing capsule-targeted phage engineering as a sustainable approach to combat CRAB. This study clarifies fundamental genetic factors that connect the modulation of phage receptors with the reduction of virulence in CRAB, highlighting an evolutionary compromise that enhances the therapeutic promise of phages aimed at the capsule in treating KL3-type <i>A. baumannii</i> infections.