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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      In this study, we characterized MDR stool-derived\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      isolates and assessed their antibiotic resistance profiles. We then isolated, characterized and evaluated the efficacy of bacteriophage vB_Eco_ZCEC15 (\u03a6ZCEC15) 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 \u03a6ZCEC15 on Caco-2 colon carcinoma cells. Furthermore, we explored the effect of bacterial lysis by \u03a6ZCEC15 on Caco-2 cell viability to optimize its therapeutic applications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Whole-genome sequencing revealed a large \u03a6ZCEC15 genome (170,313\u00a0bp) encoding 272 annotated ORFs, eight tRNAs, and multiple accessory genes. The phage exhibited remarkable stability under diverse physical stressors, including pH 3. Notably, \u03a6ZCEC15 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings highlight the potential of \u03a6ZCEC15 as a safe and effective therapeutic agent against MDR\n                      <jats:italic>E. coli<\/jats:italic>\n                      and encourage the importance of addressing resistance mechanisms to optimize clinical outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-026-04737-x","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T02:34:49Z","timestamp":1771295689000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Large-genome phage vB_Eco_ZCEC15 targets gastrointestinal MDR E. coli: evidence from in vitro and Caco-2 cell models"],"prefix":"10.1186","volume":"26","author":[{"given":"Kareem","family":"Essam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira A.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salsabil","family":"Makky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza G.","family":"Kamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"El-Shibiny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"issue":"12","key":"4737_CR1","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.3390\/ANI10122239","volume":"10","author":"S Ramos","year":"2020","unstructured":"Ramos S, Silva V, de Lurdes Enes Dapkevicius M, et al. 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