Discovery and characterisation of new phage targeting uropathogenicEscherichia coli

Abstract

ABSTRACTAntimicrobial resistance (AMR) is increasing at an escalating rate with few new therapeutic options in the pipeline. Urinary tract infections (UTIs) are one of the most prevalent bacterial infections globally and are particularly prone to becoming recurrent and antibiotic resistant. The aim of this study was to discover and characterise new bacterial viruses (phage) against uropathogenicEscherichia coli(UPEC), which is the leading cause of UTIs. Six phages from theAutographiviridaefamily andGuernseyvirinaesub-family were isolated from wastewater and sequenced. The length of the isolated phage genomes was between 39,471 bp and 45,233 bp, with a GC content between 45.0% and 51.0%, and 57 to 84 predicted coding sequences (CDS) per genome. These phages were found to infect between 25 – 75% of the twelve UPEC strains tested. Using sequence comparison and predicted structural alignments, we show a similarity between the C-terminal domain of the tail fiber proteins of two phage that correlates with their host range.In vitrocharacterisation of phage cocktails against a single bacterial strain did not perform better than the best-performing phage, but did show synergistic improvement against a mixed UPEC strain population. Lastly, we measured the effectiveness of treatment with phage with different lytic kinetics in a sequential treatment and found it was improved over single phage treatment.