{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T13:52:24Z","timestamp":1776693144537,"version":"3.51.2"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Vancomycin-resistant <jats:italic>Enterococcus faecalis<\/jats:italic> (VRE) poses a significant challenge in clinical settings due to its resistance to multiple antibiotics. Phage therapy offers a promising alternative to address this resistance crisis. However, critical gaps remain regarding optimal dosing, therapeutic design, and treatment timing for phage therapy targeting VRE-induced bacteremia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The biological and genomic characteristics of a novel lytic phage specific to VRE were investigated. Its <jats:italic>in vitro<\/jats:italic> bactericidal and antibiofilm activities were evaluated, along with its synergy with antimicrobial agents. <jats:italic>In vitro<\/jats:italic> safety and protective efficacy were assessed using a mouse bacteremia model. The impact of phage therapy on gut microbiota was examined through 16S rDNA gene sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We isolated and characterized a novel lytic phage, vB_EfaS-1017, specific to vancomycin-resistant <jats:italic>E. faecalis<\/jats:italic>. This phage features a circular, double-stranded DNA genome (40,766 bp), sharing 91.19% identity and 79% coverage with <jats:italic>Enterococcus<\/jats:italic> phage vB_EfaS_SRH2. vB_EfaS-1017 exhibited robust bactericidal and antibiofilm activity <jats:italic>in vitro<\/jats:italic> and demonstrated synergy with levofloxacin. Safety assessments confirmed its non-toxicity to mammalian cells and lack of hemolytic activity. In a mouse bacteremia model, phage treatment alone rescued 60% of infected mice, while combining phage with levofloxacin increased survival to 80%. Prophylactic administration of phage 24 hours prior to infection failed to prevent mortality. However, a combination of prophylactic phage administration and delayed treatment rescued 60% of mice, compared to 100% mortality in the delayed treatment alone group. Additionally, phage therapy helped maintain or restore gut microbiota balance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings underscore the potential of phage-antibiotic combinations as a superior therapeutic strategy against VRE infections. The observed synergy between phages and antibiotics highlights a promising approach to overcoming bacterial resistance and improving clinical outcomes. Furthermore, prophylactic phage administration may provide a critical time window for effective delayed treatment. Further preclinical research is essential to refine phage therapy protocols for clinical application.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1504696","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T07:15:45Z","timestamp":1737702945000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Prophylactic phage administration provides a time window for delayed treatment of vancomycin-resistant Enterococcus faecalis in a murine bacteremia model"],"prefix":"10.3389","volume":"15","author":[{"given":"Wei-Xiao","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao-Yang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu-Zhen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-Yong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng-Cheng","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Yao","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang-Lin","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Han","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Mei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"D517","DOI":"10.1093\/nar\/gkz935","article-title":"CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database","volume":"48","author":"Alcock","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1111\/jam.14704","article-title":"Antimicrobial susceptibility testing: currently used methods and devices and the near future in clinical practice","volume":"129","author":"Benkova","year":"2020","journal-title":"J. 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