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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1504696
This article is part of the Research Topic Novel Strategies to Target Biofilm Formation in ESKAPE Pathogens for Combating Antimicrobial Resistance View all 6 articles

Prophylactic administration of phage offers time window for delayed treatment against vancomycin-resistant Enterococcus faecalis in a murine bacteremia model

Provisionally accepted
Wei-Xiao Wang Wei-Xiao Wang 1Jiao-Yang Yu Jiao-Yang Yu 2Xiu-Zhen Chen Xiu-Zhen Chen 1Shi-Yong Fu Shi-Yong Fu 1Hui Li Hui Li 3Peng-Cheng Yi Peng-Cheng Yi 1Yun-Yao Ren Yun-Yao Ren 1Shuang-Lin Gu Shuang-Lin Gu 1Jing-Han Gao Jing-Han Gao 1Jing Fan Jing Fan 1Yan-Mei Sun Yan-Mei Sun 2Jie Feng Jie Feng 4Shiwei Wang Shiwei Wang 2Wei Chen Wei Chen 1*
  • 1 Nanjing University of Chinese Medicine, Nanjing, China
  • 2 Northwest University, Xi'an, China
  • 3 Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
  • 4 Chinese Academy of Sciences (CAS), Beijing, Beijing, China

The final, formatted version of the article will be published soon.

    Vancomycin-resistant Enterococcus faecalis (VRE) presents a significant challenge in clinical settings due to its resistance to multiple antibiotics. In this study, we isolated and characterized a novel lytic phage, vB_EfaS-1017, specific to vancomycin-resistant E. faecalis. The phage had a circular double-stranded DNA genome of 40,766 bp, sharing 91.19% identity and 79% coverage with Enterococcus phage vB_EfaS_SRH2. vB_EfaS-1017 demonstrated strong bactericidal activity in vitro, effective inhibition and eradication of biofilms, and synergistic interaction with levofloxacin. Safety evaluations indicated that vB_EfaS-1017 is non-toxic to mammalian cells and does not cause hemolysis. In a bacteremia mouse model, phage administration alone rescued 60% of mice, whereas a combination of phage and levofloxacin rescued 80%. Notably, prophylactic administration of phage 24 hours before infection did not 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. Phage therapy can not only target the pathogenic bacteria but also help maintain or restore the ecological balance of the microbiota. These findings highlight the potential of phageantibiotic combinations as a superior therapeutic strategy against VRE infections. The synergy between phages and antibiotics offers a promising approach to overcoming bacterial resistance and achieving better clinical outcomes. Additionally, prophylactic use of phages can provide a critical time window for effective delayed treatment. Further research and preclinical trials are warranted to optimize phage therapy protocols for clinical application.

    Keywords: Vancomycin-resistant enterococcus faecalis, phage therapy, Synergy, Prophylactic administration, Bacteremia, Mouse

    Received: 01 Oct 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Wang, Yu, Chen, Fu, Li, Yi, Ren, Gu, Gao, Fan, Sun, Feng, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Wei Chen, Nanjing University of Chinese Medicine, Nanjing, China

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