Repurposing Drugs as Bacteroides fragilis BFT-3 Inhibitors in the Animal Infection Model Galleria mellonella

Jiménez-Alesanco, Ana (Universidad de Zaragoza) ; Gómara-Lomero, Marta ; Jeblaoui, Hajar ; Vega, Sonia (Universidad de Zaragoza) ; Velázquez-Campoy, Adrián (Universidad de Zaragoza) ; Aínsa, José Antonio (Universidad de Zaragoza) ; Abián, Olga (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1111/nyas.70255

Año: 2026

Publicado en: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1557, 1 (2026), 16
ISSN: 0077-8923

Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2021-127296OB-I00
Financiación: info:eu-repo/grantAgreement/ES/DGA/B08-24R
Financiación: info:eu-repo/grantAgreement/ES/DGA/B25-23R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI18-00349
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI20-00661
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI21-00394
Financiación: info:eu-repo/grantAgreement/ES/MCIU/PID2024-160408OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN-AEI/PRTR-C17.I1
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Microbiología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Área RPT Laboral BIFI (Institutos Univ. de Investig.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)