4-Hydroxycoumarin inhibits biofilm formation and enhances antibiotic efficacy against Escherichia coli O157:H7
Abstract
Background: Conventional bactericidal antibiotics often fail to eradicate Escherichia coli O157:H7 ( E. coli O157) infections due to biofilm-mediated antimicrobial tolerance, and monotherapy can inadvertently drive resistance selection. This study aimed to identify compounds capable of modulating LuxS/AI-2-related phenotypes and to evaluate their potential to disrupt biofilms and enhance antibiotic efficacy against E. coli O157.
Methods: The effects of 4-HC on biofilm formation, extracellular polymeric substance (EPS) biosynthesis, and flagella-mediated motility were assessed in vitro. Antibiotic potentiation was evaluated through combination assays across multiple antibiotic classes. In vivo efficacy was tested in a murine systemic infection model, with qualitative histological observation used to evaluate splenic, hepatic, and ileal tissue damage.
Results: 4-HC disrupted biofilm formation by suppressing EPS biosynthesis and flagella-mediated motility, thereby destabilizing biofilm architecture and impairing bacterial dissemination. 4-HC acted as a broad-range potentiator for most antibiotics tested, with the most pronounced effect observed in combination with fosfomycin sodium. This combination reduced systemic bacterial burden and restored intestinal barrier function in vivo . In the murine model, the 4-HC–fosfomycin regimen improved survival and markedly attenuated splenic necrosis and ileal tissue damage, with efficacy superior to monotherapy.
Conclusion: 4-HC disrupts biofilm formation and enhances antibiotic efficacy against E. coli O157 infection, supporting the strategy of combining biofilm-modulating adjuvants with conventional antibiotics to combat antimicrobial resistance. However, rigorous safety evaluation is required before clinical translation.
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BibTeX
@article{zhang20264hydroxycoumarin,
title = {{4-Hydroxycoumarin inhibits biofilm formation and enhances antibiotic efficacy against Escherichia coli O157:H7}},
author = {Hongxing Zhang and Jing Xu and Yaxin Zhou and Zhijin Zhang and Zixuan Shang and Bing Li and Yubin Bai and Jiyu Zhang},
journal = {Frontiers in microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1934000},
url = {https://europepmc.org/article/PMC/PMC13669101},
note = {CC BY},
}
RIS
TY - JOUR
TI - 4-Hydroxycoumarin inhibits biofilm formation and enhances antibiotic efficacy against Escherichia coli O157:H7
AU - Hongxing Zhang
AU - Jing Xu
AU - Yaxin Zhou
AU - Zhijin Zhang
AU - Zixuan Shang
AU - Bing Li
AU - Yubin Bai
AU - Jiyu Zhang
PY - 2026
DA - 2026/10/01
JO - Frontiers in microbiology
DO - 10.3389/fmicb.2026.1934000
UR - https://europepmc.org/article/PMC/PMC13669101
AB - Background: Conventional bactericidal antibiotics often fail to eradicate Escherichia coli O157:H7 ( E. coli O157) infections due to biofilm-mediated antimicrobial tolerance, and monotherapy can inadvertently drive resistance selection. This study aimed to identify compounds capable of modulating LuxS/AI-2-related phenotypes and to evaluate their potential to disrupt biofilms and enhance antibiotic efficacy against E. coli O157. Methods: The effects of 4-HC on biofilm formation, extracellular polymeric substance (EPS) biosynthesis, and flagella-mediated motility were assessed in vitro. Antibiotic potentiation was evaluated through combination assays across multiple antibiotic classes. In vivo efficacy was tested in a murine systemic infection model, with qualitative histological observation used to evaluate splenic, hepatic, and ileal tissue damage. Results: 4-HC disrupted biofilm formation by suppressing EPS biosynthesis and flagella-mediated motility, thereby destabilizing biofilm architecture and impairing bacterial dissemination. 4-HC acted as a broad-range potentiator for most antibiotics tested, with the most pronounced effect observed in combination with fosfomycin sodium. This combination reduced systemic bacterial burden and restored intestinal barrier function in vivo . In the murine model, the 4-HC–fosfomycin regimen improved survival and markedly attenuated splenic necrosis and ileal tissue damage, with efficacy superior to monotherapy. Conclusion: 4-HC disrupts biofilm formation and enhances antibiotic efficacy against E. coli O157 infection, supporting the strategy of combining biofilm-modulating adjuvants with conventional antibiotics to combat antimicrobial resistance. However, rigorous safety evaluation is required before clinical translation.
SN - 1664-302X
ER -