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        <identifier>oai:figshare.com:article/34039716</identifier>
        <datestamp>2026-10-01T05:43:17Z</datestamp>
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          <dc:title>Supplementary file 1_4-Hydroxycoumarin inhibits biofilm formation and enhances antibiotic efficacy against Escherichia coli O157:H7.docx</dc:title>
          <dc:creator>Hongxing Zhang (209372)</dc:creator>
          <dc:creator>Jing Xu (15337)</dc:creator>
          <dc:creator>Yaxin Zhou (4768866)</dc:creator>
          <dc:creator>Zhijin Zhang (204027)</dc:creator>
          <dc:creator>Zixuan Shang (13987303)</dc:creator>
          <dc:creator>Bing Li (43671)</dc:creator>
          <dc:creator>Yubin Bai (1350858)</dc:creator>
          <dc:creator>Jiyu Zhang (725001)</dc:creator>
          <dc:subject>Microbiology</dc:subject>
          <dc:subject>4-hydroxycoumarin</dc:subject>
          <dc:subject>biofilm</dc:subject>
          <dc:subject>Escherichia coli O157:H7</dc:subject>
          <dc:subject>LuxS</dc:subject>
          <dc:subject>QS</dc:subject>
          <dc:description>Background&lt;p&gt;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.&lt;/p&gt;Methods&lt;p&gt;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.&lt;/p&gt;Results&lt;p&gt;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.&lt;/p&gt;Conclusion&lt;p&gt;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.&lt;/p&gt;</dc:description>
          <dc:date>2026-10-01T05:43:17Z</dc:date>
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          <dc:identifier>10.3389/fmicb.2026.1934000.s001</dc:identifier>
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          <dc:rights>CC BY 4.0</dc:rights>
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