{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:00:49Z","timestamp":1790834449733,"version":"4.1.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Conventional bactericidal antibiotics often fail to eradicate Escherichia coli O157:H7 (\n                      <jats:italic>E. coli<\/jats:italic>\n                      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\n                      <jats:italic>E. coli<\/jats:italic>\n                      O157.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>in vivo<\/jats:italic>\n                      . In the murine model, the 4-HC\u2013fosfomycin regimen improved survival and markedly attenuated splenic necrosis and ileal tissue damage, with efficacy superior to monotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      4-HC disrupts biofilm formation and enhances antibiotic efficacy against\n                      <jats:italic>E. coli<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1934000","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:42:40Z","timestamp":1790833360000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["4-Hydroxycoumarin inhibits biofilm formation and enhances antibiotic efficacy against Escherichia coli O157:H7"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongxing","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, New Veterinary Drugs Engineering Research Center of Gansu Province, Key Laboratory of New Veterinary Drugs Engineering of CAAS, Laboratory Animal Science Data Center of Gansu Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, New Veterinary Drugs Engineering Research Center of Gansu Province, Key Laboratory of New Veterinary Drugs Engineering of CAAS, Laboratory Animal Science Data Center of Gansu Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, New Veterinary Drugs Engineering Research Center of Gansu Province, Key Laboratory of New Veterinary Drugs Engineering of CAAS, Laboratory Animal Science Data Center of Gansu Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, New Veterinary Drugs Engineering Research Center of Gansu Province, Key Laboratory of New Veterinary Drugs Engineering of CAAS, Laboratory Animal Science Data Center of Gansu Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS","place":["Lanzhou, Gansu, China"]},{"name":"College of Life Science and Food Engineering, Hebei University of Engineering","place":["Handan, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Shang","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, New Veterinary Drugs Engineering Research Center of Gansu Province, Key Laboratory of New Veterinary Drugs Engineering of CAAS, Laboratory Animal Science Data Center of Gansu Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS","place":["Lanzhou, Gansu, China"]},{"name":"College of Life Science and Food Engineering, Hebei University of Engineering","place":["Handan, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, New Veterinary Drugs Engineering Research Center of Gansu Province, Key Laboratory of New Veterinary Drugs Engineering of CAAS, Laboratory Animal Science Data Center of Gansu Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubin","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, New Veterinary Drugs Engineering Research Center of Gansu Province, Key Laboratory of New Veterinary Drugs Engineering of CAAS, Laboratory Animal Science Data Center of Gansu Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, New Veterinary Drugs Engineering Research Center of Gansu Province, Key Laboratory of New Veterinary Drugs Engineering of CAAS, Laboratory Animal Science Data Center of Gansu Province, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1001\/archinte.1986.00360210235037","article-title":"Cholestatic hepatic injury related to warfarin exposure","volume":"146","author":"Adler","year":"1986","journal-title":"Arch. 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