Combination of phage PH826 and antibiotics inhibits biofilm formation of multidrug-resistant Pseudomonas aeruginosa

Abstract:

[Objective] Pseudomonas aeruginosa is a major Gram-negative pathogen that can exacerbate lung infections in the patients with cystic fibrosis, which can ultimately lead to death. The emerging multi-drug resistant and pan-drug resistant strains pose challenges to the prevention and control of P. aeruginosa infection. [Methods] A phage capable of lysing multi-drug resistant P. aeruginosa was isolated from farm sewage. The morphological characteristics, biological characteristics, host range, genomic features, and in vitro inhibitory ability of the isolate were studied. The biofilm inhibition test was conducted with both the phage and antibiotics. [Results] The phage PH826 was identified to be a member of the genus Nankokuvirus and it can keep stability within a wide temperature range from 4℃ to 60℃ and pH range (pH 3.0-11.0). The host range test showed that PH826 could lyse 13 P. aeruginosa strains from human and animals. The antibacterial test in vitro showed that PH826 was strongly lytic against P. aeruginosa at multiplicity of infection (MOI) of 10, 1, and 0.1. The genome of PH826 was 87 956 bp in length, with the G+C content of 54.70%, encoding 165 open reading frames (ORFs) including an endolysin gene. The combination of PH826 at 1×MIC (minimum inhibitory concentration, MIC), 2×MIC, or 4×MIC and ciprofloxacin reduced biofilm formation by more than 80% at the time points of 24 h and 48 h. The combination of PH826 at 2×MIC or 4×MIC and meropenem reduced biofilm formation by more than 80% at the time points of 24 h and 48 h. [Conclusion] PH826 may be a potential disinfectant and therapeutic agent that can be used alone or in combination with antibiotics for the prevention and treatment of pathogenic P. aeruginosa.