Significant variability in virulence factors and antibiotic resistance of uropathogenic Escherichia coli strains may be counteracted by their susceptibility to lytic bacteriophages

Abstract

Uropathogenic Escherichia coli (UPEC) strains are the primary cause of urinary tract infections and pose a serious clinical problem due to their remarkable genetic variability, diverse virulence traits, and rapidly increasing antibiotic resistance. In this study, five clinical UPEC isolates (EC3, EC149, EC164, EC179, and EC256) were deeply investigated to better understand their pathogenic potential. The strains differed substantially in genome architecture, mobile genetic elements, plasmid composition, virulence factors composition, and antibiotic resistance profiles, illustrating the highly dynamic nature of UPEC populations. Of particular concern was the detection of plasmids linked to resistance against “last-resort” antibiotics, emphasizing the growing epidemiological risk associated with these pathogens. To address the limitations of conventional therapy, five lytic bacteriophages active against the analyzed UPEC strains were isolated and thoroughly characterized. Comparative genomic and phylogenetic analyses revealed that all phages represent previously undescribed species belonging to the genera Hanrivervirus, Warwickvirus, Nonavirus, Kagunavirus, and Vectrevirus. Functional assays demonstrated pronounced differences in host range and infectivity. Among them, phage vB_EcoS-149_4M emerged as the most promising candidate, combining broad antibacterial activity with high stability and a favourable safety profile, including the absence of toxin or antibiotic resistance genes and no detectable cytotoxicity toward human cell lines. Taken together, these findings highlight both the complexity and clinical threat posed by UPEC strains and the substantial potential of carefully selected bacteriophages as effective and precise antimicrobial tools. In effect, this multi-faceted approach provides a strong foundation for the development of precision phage therapy against multidrug-resistant UPEC infections.