Growth Characteristics of Bacteriophage Mimir124 on UPEC N124: Potential of Ecological Adaptation

Abstract Bacteriophage Mimir124, a virulent N4-like phage isolated against a multidrug-resistant uropathogenic E. coli (UPEC) strain N124 (O101 serotype), exhibits unusual phenotypic heterogeneity during plaque formation. Under standard conditions (37°C), Mimir124 produces two stable plaque morphotypes: small (1–2 mm, transparent, sharp-edged) and large (4–10 mm, surrounded by an expanding enzymatic halo). Whole-genome sequencing revealed that this dichotomy presumably stems from mutations in the tail fiber protein gene: a six-amino-acid in-frame deletion in the “large” variant and a premature stop codon in the “small” variant. The halo formation is believed to be due to the phage-encoded depolymerase activity, enabling diffusion-mediated enzymatic cell lysis beyond the primary plaque and maintaining infectivity even at low temperatures (4°C). However, viable phage particles were found within the halo zone up to 25 mm from the plaque center, suggesting enhanced ecological adaptability, particularly the ability to infect metabolically inactive or stationary-phase bacteria—a feature of high relevance for personalized phage therapy against persistent or relapsing urological infections. The sequencing of the phage sub-strains with large- and small-plaque phenotypes revealed the deletion.