Characterization of newly isolated bacteriophage to control multi-drug resistant Pseudomonas aeruginosa colonizing incision wounds in a rat model: in vitro and in vivo approach

Life Sci. 2022 Dec 1:310:121085. doi: 10.1016/j.lfs.2022.121085. Epub 2022 Oct 17.

Abstract

Aims: Pseudomonas aeruginosa is one of the most common causes of opportunistic and hospital-acquired infections in the world, which is repeatedly associated with treatment challenges. The evolution of new approaches such as phage therapy may be a novel alternative strategy for the treatment of these life-threatening infections. This paper aims to characterize the isolated bacteriophage and evaluate its potential therapy for the treatment of induced skin infection.

Main methods: Enrichment method and double-layer overlay agar were used for isolation and purification of bacteriophages. The lysis profiles of isolated phages were evaluated using spot method. The phage morphology was visualized by transmission electron microscope. The growth kinetics such as adsorption rate, latent period, burst size, and in vitro challenging activity were determined. Biofilm eradication was analyzed using confocal laser scanning microscope (CLSM). Furthermore, the potential activity of phage therapy was evaluated in a rat model.

Key findings: Eight phages were isolated while phage phPS127 displayed the strongest lytic spectra. This phage is a member of Siphoviridae family that showed good growth kinetics. Our in vitro results showed that phage phPS127 significantly decreased the bacterial density (P < 0.05). CLSM revealed the significant reduction in the viability of the biofilm-adhered cells (P < 0.05). Phage therapy provided a significant level of treatment and promoted wound healing. Moreover, phage therapy significantly decreased bacterial burden (P < 0.05), inflammatory cytokine (TNF-α) and apoptosis (caspase-3) expression level.

Significance: Phage phPS127 can be considered as a promising candidate for treatment of clinical P. aeruginosa infections.

Keywords: Antibiotics; Biofilm; Multiple-drug resistance; P. aeruginosa; Phage therapy; Skin infection.

MeSH terms

  • Animals
  • Bacteriophages*
  • Biofilms
  • Pseudomonas Phages*
  • Pseudomonas aeruginosa
  • Rats