Characterization of Novel Straboviridae Phages Enhancing Antibiotic Efficacy and Biofilm Inhibition Against MDR Escherichia coli

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Abstract

Multidrug-resistant Escherichia coli (MDR- E. coli ) is a significant public health concern due to its resistance to multiple antibiotics, which complicates infection treatment. Phages are gaining attention for their specific lytic activity against pathogenic bacteria. This study aimed to isolate and characterize lytic bacteriophages designated as EC.W1-1 and EC.W15-3, targeting different sequence types (STs) of multidrug-resistant E. coli . The isolated phages, EC.W1-1 and EC.W15-3, belonged to the Straboviridae family and the genus Tequatrovirus . Phages remained stable at pH 2–10 for 4h and below 80°C for 1h. They exhibited in vitro bacterial lytic activity at various MOIs (10–0.001). The one-step growth curve of phages showed a short latent period of about 10–15 min and a moderate burst size of 64–83 (pfu/cell). Phages genome size ranged from 37,736–123,792bp, with G + C content of 35.6–37.2%. No virulence or drug-resistance genes were detected, enhancing their safety profile. Most predicted coding sequences (CDSs) in the phages analyzed were associated with various putative functions like tail protein, holin, lysis protein, head protein, structural proteins, and DNA replication, transcription, and repair proteins. Furthermore, the study explored the combined effects of phages and antibiotics, showing effective inhibition of ESBL-producing and carbapenem-resistant E. coli (CREC) with sub-lethal antibiotic doses. In addition, phages suspensions can eliminate biofilm formed against different STs of MDR E. coli . Therefore, we concluded that EC.W1-1 and EC.W15-3 have potential therapeutic properties, providing an alternative to antibiotic for treating various pathogenic MDR E. coli sequence types.

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