170420 20260420103355.0 doi 10.1111/nyas.70255 sideral 148888 ART-2026-148888 eng Jiménez-Alesanco, Ana Universidad de Zaragoza (orcid)0000-0003-4726-7821 Repurposing Drugs as Bacteroides fragilis BFT-3 Inhibitors in the Animal Infection Model Galleria mellonella 2026 Bacteroides fragilis is a key component of the human gut microbiota, although enterotoxigenic strains (ETBF), which produce B. fragilis toxin (BFT), can act as opportunistic pathogens. BFT disrupts intestinal epithelial integrity and contributes to conditions such as inflammatory bowel disease and colorectal cancer. This study aimed to characterize three allosteric inhibitors of BFT-3 (isoform 3 of BFT), previously identified by our group through high-throughput screening of US Food and Drug Administration approved drugs. We evaluated their activities in vitro and in vivo. Using Galleria mellonella larvae as a novel infection model for B. fragilis, we assessed the antimicrobial and antivirulence potential of these compounds. Among the three tested compounds, MOA4 demonstrated superior efficacy, enhanced bacterial clearance in vivo, and increased larval survival in a dose-dependent manner, with minimal toxicity. Synergy studies have revealed the potential combinatory effects of MOA4 and conventional antibiotics. These findings establish G. mellonella as a valuable alternative model for studying B. fragilis infections and highlight MOA4 as a promising candidate to be repurposed for the treatment of B. fragilis-mediated diseases while preserving commensal microbiota. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/AEI/PID2021-127296OB-I00 info:eu-repo/grantAgreement/ES/DGA/B08-24R info:eu-repo/grantAgreement/ES/DGA/B25-23R info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI18-00349 info:eu-repo/grantAgreement/ES/ISCIII/PI20-00661 info:eu-repo/grantAgreement/ES/ISCIII/PI21-00394 info:eu-repo/grantAgreement/ES/MCIU/PID2024-160408OB-I00 info:eu-repo/grantAgreement/ES/MICINN-AEI/PRTR-C17.I1 info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Gómara-Lomero, Marta Jeblaoui, Hajar Vega, Sonia Universidad de Zaragoza (orcid)0000-0002-1232-6310 Velázquez-Campoy, Adrián Universidad de Zaragoza (orcid)0000-0001-5702-4538 Aínsa, José Antonio Universidad de Zaragoza (orcid)0000-0003-2076-844X Abián, Olga Universidad de Zaragoza (orcid)0000-0001-5664-1729 1011 630 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Microbiología 0 X Universidad de Zaragoza Institutos Univ. de Investig. Área RPT Laboral BIFI 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1557, 1 (2026), 16 Ann. N.Y. Acad. Sci. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 0077-8923 1867841 http://zaguan.unizar.es/record/170420/files/texto_completo.pdf Versión publicada 2503900 http://zaguan.unizar.es/record/170420/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:170420 articulos driver 2026-04-18-10:49:14 ARTICLE