{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:52:27Z","timestamp":1787961147727,"version":"build-2784847793"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["515454"],"award-info":[{"award-number":["515454"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022019","name":"Qbiotics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022019","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,2,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n The unrestricted use of colistin in animal husbandry has led to the emergence of mobile plasmid-borne colistin resistance (\n mcr<\/jats:italic>\n ). The antimicrobial epoxytigliane, EBC-1013, has been shown to be effective in the topical treatment of biofilm-mediated infections\n in vivo<\/jats:italic>\n . Hypothesizing that EBC-1013 interacts with the modified bacterial outer membrane of colistin-resistant\n Escherichia coli,<\/jats:italic>\n we investigated its ability to potentiate the activity of colistin using fractional inhibitory concentration (FIC) index determinations against environmental\n mcr<\/jats:italic>\n Enterobacteriaceae. Molecular dynamics (MD) simulations were used to visualize EBC-1013 interactions with the outer membrane\n in silico<\/jats:italic>\n . Modification of outer membrane surface chemistry and adhesion properties was characterized using X-ray photoelectron spectroscopy (XPS) and hydrophobicity and bacterial membrane permeability assays. Anti-biofilm activity was quantified using confocal laser scanning microscopy (CLSM). Checkerboard assays revealed synergistic effects of EBC-1013 with colistin (FIC \u2264 0.5) in 6\/9 strains. MD simulations demonstrated weak EBC-1013 interactions with colistin and the outer membrane. XPS suggested modification of the outer membrane in both colistin-sensitive and colistin-resistant\n E. coli,<\/jats:italic>\n as well as the interaction of colistin and EBC-1013 with the phosphoethanolamine (pEtN)-substituted\n mcr<\/jats:italic>\n lipid moiety. EBC-1013 binding significantly decreased bacterial hydrophilicity and potentiated membrane permeability induced by colistin (\n P<\/jats:italic>\n < 0.05). In the biofilm model, potentiation was also evident, with a marked decrease in bacterial biomass in EBC-1013\/colistin combined treatments (\n P<\/jats:italic>\n < 0.0001) for colistin-resistant\n E. coli<\/jats:italic>\n . The results highlight the ability of EBC-1013 to modify the bacterial membrane of colistin-resistant\n E. coli<\/jats:italic>\n and potentiate the activity of colistin in the treatment of multidrug-resistant wound bacteria.\n <\/jats:p>\n <\/jats:sec>\n \n IMPORTANCE<\/jats:title>\n \n Resistance to colistin, an antibiotic of last resort for hard-to-treat infections, is on the increase. Therefore, the need to develop new antimicrobials to tackle antimicrobial resistance is of paramount importance. The epoxytiglianes represent an exciting range of molecules with a diverse range of biological effects in human and veterinary applications, including antimicrobial properties. In this study, we show how EBC-1013 interacts with the outer surface of colistin-resistant\n Escherichia coli<\/jats:italic>\n cells, inducing chemical and structural changes to the cell wall, making it susceptible again to colistin treatment. This ability of EBC-1013 to enhance the activity of colistin against a range of colistin-resistant\n E. coli<\/jats:italic>\n suggests that EBC-1013, alone (or as a combination therapy), has potential as a new treatment strategy to treat antibiotic-resistant bacterial wound infections and reduce antibiotic usage.\n <\/jats:p>\n \n This study is registered with ClinicalTrials.gov as (Australian New Zealand Clinical Trials Register:\n ACTRN12624000544572<\/jats:ext-link>\n ).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/mbio.02314-25","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T13:00:26Z","timestamp":1767013226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Epoxytiglianes potentiate the activity of colistin against resistant\n Escherichia coli<\/i>\n via modification of the bacterial cell 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