Abstract Background Bacterial resistance to traditional antibiotics is spreading at an alarming rate, threatening public health and various industrial applications. Phage therapy has emerged as a promising alternative for combating multidrug-resistant (MDR) bacterial infections. However, most studies have focused on in vitro interactions, often overlooking phage dynamics within human cell environments. Methodology In this study, we characterized MDR stool-derived Escherichia coli isolates and assessed their antibiotic resistance profiles. We then isolated, characterized and evaluated the efficacy of bacteriophage vBEcoZCEC15 (ΦZCEC15) against selected strains under optimized culture conditions (pH 7. 3) and acidic conditions mimicking the human gastrointestinal tract. To assess host safety, we tested the impact of ΦZCEC15 on Caco-2 colon carcinoma cells. Furthermore, we explored the effect of bacterial lysis by ΦZCEC15 on Caco-2 cell viability to optimize its therapeutic applications. Results Whole-genome sequencing revealed a large ΦZCEC15 genome (170, 313 bp) encoding 272 annotated ORFs, eight tRNAs, and multiple accessory genes. The phage exhibited remarkable stability under diverse physical stressors, including pH 3. Notably, ΦZCEC15 achieved optimal antibacterial activity at a low multiplicity of infection (MOI 0. 1), efficiently reducing bacterial titers without compromising eukaryotic host cell viability. In contrast, untreated bacterial infections induced cytotoxic effects in Caco-2 cells. Conclusion These findings highlight the potential of ΦZCEC15 as a safe and effective therapeutic agent against MDR E. coli and encourage the importance of addressing resistance mechanisms to optimize clinical outcomes.
Essam et al. (Tue,) studied this question.