Bacteriophage cocktail and phage antibiotic synergism as promising alternatives to conventional antibiotics for the control of multi-drug-resistant uropathogenic Escherichia coli

Virus Res. 2021 Sep:302:198496. doi: 10.1016/j.virusres.2021.198496. Epub 2021 Jun 25.

Abstract

Infections related to antibiotic resistant bacteria are accelerating on a global scale, and hence to encounter this problem in case of urinary tract infections; bacteriophages were isolated for biocontrol of multi-drug resistant (MDR) uropathogenic Escherichia coli (UPECs) isolates. Four lytic phages were purified, characterized, and evaluated for their effectiveness in the form of cocktail and in synergy with antibiotics. Morphological features and other life cycle specifications of phages revealed that two phages Escherichia phage FS11 and Escherichia phage FS17 belonged to Myoviridae and the other two phages Escherichia phage PS8 and Escherichia phage PS6 belonged to Siphoviridae family of order Caudovirales. One step growth curve analysis demonstrated that phage FS11 and phage FS17 had latent time of 24 min and 26 min, and a burst size of ~121 and 98 phage particles/ cell respectively; while for phage PS8 and phage PS6, the latent time was 42 min and 35 min, and the burst size was 87 and 78 particles/ cell, respectively; depicting the lytic nature of phages. The use of all four phages together in the form of a cocktail resulted into a considerable enhancement in the lytic ability; the phage cocktail lysed 86.7% of the clinical isolates, compared to lysis in the range of 50%-66% by individual phages. Studies on in vitro evaluation of phage-antibiotic combinations revealed synergism between antibiotics and the phage cocktail (phage PS6 and phage FS17), wherein the phage cocktail was observed to efficiently inhibit the strains in the presence of sub-lethal doses of antibiotics. The study thus concludes that the use of multiple phages and phage-antibiotic combinations could prove beneficial in the era of rapidly increasing drug-resistant strains.

Keywords: Multi-drug resistance; Phage cocktail; Phage-antibiotic synergism; UPECs; UTIs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacteriophages*
  • Humans
  • Phage Therapy* / methods
  • Urinary Tract Infections* / microbiology
  • Urinary Tract Infections* / therapy
  • Uropathogenic Escherichia coli*

Substances

  • Anti-Bacterial Agents