Therapeutic effect and anti-biofilm ability assessment of a novel phage, phiPA1-3, against carbapenem-resistant Pseudomonas aeruginosa

Virus Res. 2023 Oct 2:335:199178. doi: 10.1016/j.virusres.2023.199178. Epub 2023 Aug 3.

Abstract

Multiple drug-resistant (MDR) Pseudomonas aeruginosa commonly causes severe hospital-acquired infections. The gradual emergence of carbapenem-resistant P. aeruginosa has recently gained attention. A wide array of P. aeruginosa-mediated pathogenic mechanisms, including its biofilm-forming ability, limits the use of effective antimicrobial treatments against it. In the present study, we isolated and characterized the phenotypic, biological, and genomic characteristics of a bacteriophage, vB_PaP_phiPA1-3 (phiPA1-3). Biofilm eradication and phage rescue from bacterial infections were assessed to demonstrate the efficacy of the application potential. Host range spectrum analysis revealed that phiPA1-3 is a moderate host range phage that infects 20% of the clinically isolated strains of P. aeruginosa tested, including carbapenem-resistant P. aeruginosa (CRPA). The phage exhibited stability at pH 7.0 and 9.0, with significantly reduced viability below pH 5.0 and beyond pH 9.0. phiPA1-3 is a lytic phage with a burst size of 619 plaque-forming units/infected cell at 37 °C and can effectively lyse bacteria in a multiplicity of infection-dependent manner. The genome size of phiPA1-3 was found to be 73,402 bp, with a G+C content of 54.7%, containing 93 open reading frames, of which 62 were annotated as hypothetical proteins and the remaining 31 had known functions. The phage possesses several proteins similar to those found in N4-like phages, including three types of RNA polymerases. This study concluded that phiPA1-3 belongs to the N4-like Schitoviridae family, can potentially eradicate P. aeruginosa biofilms, and thus, serve as a valuable tool for controlling CRPA infections.

Keywords: Anti-biofilm; Carbapenem-resistant P. aeruginosa; N4-like phages; Phage therapy; Schitoviridae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophages*
  • Carbapenems / pharmacology
  • Genomics
  • Pseudomonas Phages* / genetics
  • Pseudomonas aeruginosa / genetics

Substances

  • Carbapenems