Enhanced antibacterial effect of a novel Friunavirus phage vWU2001 in combination with colistin against carbapenem-resistant Acinetobacter baumannii

Phitchayapak Wintachai,Rattanaruji Pomwised,Komwit Surachat,Ampapan Naknaen,Supayang Piyawan Voravuthikunchai,Sittiruk Roytrakul,Narumon Phaonakrop,Duncan R Smith

doi:10.1038/s41598-022-06582-0

Abstract

The emergence of carbapenem-resistant Acinetobacter baumannii (CRAB) has been increasingly reported, leading to greater challenges in treating infections. With the development of phage therapy and phage-antibiotic combinations, it is promising to improve the treatment of bacterial infections. In the present study, a novel vB_AbaP_WU2001 (vWU2001) phage-specific CRAB with a genome of 40,792 bp was isolated. Genomic analysis disclosed that it belongs to the Autographiviridae family of the order Caudovirales. Phage vWU2001 had a broad host range with a high adsorption rate, short latent period, large burst size and good stability. The phage could reduce preformed biofilms and inhibit biofilm formation. The combination of phage vWU2001 and colistin had significantly higher bacterial growth inhibition activity than that of phage, or colistin alone. The efficacy of the combined treatment was also evaluated in Galleria mellonella. Evaluation of its therapeutic potential showed that the combination of phage and colistin resulted in a significantly greater increase in G. mellonella survival and in bacterial clearance, as compared with that of phage or colistin alone, indicating that the combination was synergistic against CRAB. The results demonstrated that phage vWU2001 has the potential to be developed as an antibacterial agent.

Highlights

Acinetobacter baumannii, an important pathogen in the ESKAPE group, is a gram-negative coccobacillus that is associated with both nosocomial and community-acquired infections
Following the Kropinski system, the prefix vB indicates a bacterial virus, Aba denotes A. baumannii and P denotes the morphological characteristic of Podoviridae
A. baumannii is frequently involved in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP)

Summary

Introduction

Acinetobacter baumannii, an important pathogen in the ESKAPE group, is a gram-negative coccobacillus that is associated with both nosocomial and community-acquired infections. Bacteriophages (phages), viruses that infect and replicate in bacterial cells, are considered to be an alternative treatment in the post-antibiotic e ra[11,12]. The successful treatment of a multi-drug resistant (MDR) A. baumannii infected patient with a phage cocktail has been reported, with the MDR A. baumannii infection eliminated and the patient recovering[23]. This case caused an increase of interest in the development of phage therapy for patients. The combination efficacy of phage and colistin in contrast to a control CRAB infection was evaluated in vitro and G. mellonella larvae were used as an in vivo model

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