{"title":"4-Hydroxycoumarin inhibits biofilm formation and enhances antibiotic efficacy against <i>Escherichia coli</i> O157:H7.","authors":"Hongxing Zhang, Jing Xu, Yaxin Zhou, Zhijin Zhang, Zixuan Shang, Bing Li, Yubin Bai, Jiyu Zhang","doi":"10.3389/fmicb.2026.1934000","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Conventional bactericidal antibiotics often fail to eradicate Escherichia coli O157:H7 (<i>E. coli</i> 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 <i>E. coli</i> O157.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>in vivo</i>. 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.</p><p><strong>Conclusion: </strong>4-HC disrupts biofilm formation and enhances antibiotic efficacy against <i>E. coli</i> 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.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"17 ","pages":"1934000"},"PeriodicalIF":5.8000,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669101/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmicb.2026.1934000","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
背景：由于生物膜介导的抗菌素耐受性，传统的杀菌抗生素往往不能根除大肠杆菌O157:H7 （E. coli O157）感染，而单药治疗可能无意中推动耐药性选择。本研究旨在鉴定能够调节LuxS/ ai -2相关表型的化合物，并评估其破坏生物膜和增强对大肠杆菌O157的抗生素疗效的潜力。方法：体外观察4-HC对生物膜形成、细胞外聚合物质（EPS）生物合成和鞭毛介导运动的影响。通过多种抗生素类别的联合试验来评估抗生素的增强作用。在小鼠全身性感染模型中测试了体内疗效，并通过定性组织学观察来评估脾、肝和回肠组织损伤。结果：4-HC通过抑制EPS生物合成和鞭毛介导的运动来破坏生物膜的形成，从而破坏生物膜结构并损害细菌传播。4-HC作为大多数抗生素的宽范围增强剂，与磷霉素钠联合使用时效果最显著。这种组合减少了体内的系统细菌负担，恢复了肠道屏障功能。在小鼠模型中，4- hc -磷霉素方案提高了生存率，显著减轻了脾坏死和回肠组织损伤，疗效优于单药治疗。结论：4-HC破坏生物膜的形成，增强抗生素对大肠杆菌O157感染的疗效，支持生物膜调节佐剂与常规抗生素联合使用的策略，以对抗抗生素耐药性。然而，临床转化前需要严格的安全性评估。
期刊介绍：
Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Martin G. Klotz at Washington State University is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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