Phage-Antibiotic Combinations Against Klebsiella pneumoniae

hvKP ATCC43816 and its lytic phage H5 were employed as a phage-antibiotic combination model. Based on the comprehensive characterization of phages, including cryo-electron microscopy, we evaluated the synergic effect of H5 on bacterial killing in vitro when combined with multiple antibiotics, and analyzed the advantages of phage-antibiotic combinations from an evolutionary perspective and proposes a novel PAS mechanism by using ceftazidime as an example. To investigate the underlying resistance mechanisms of Kpn 43816 against single phage stress and phage-antibiotic combination stress, we performed RNA-Seq analysis on four strains under different stress conditions: CP17, which is resistant to the phage-antibiotic combination but shows no mutations in the genome; CP6, which is resistant to the phage-antibiotic combination and contains a wcaJ mutation; P2 and P13, which are resistant to phage only and contain wcaJ mutations; and wild-type strains.