Artículo
Engineered toxin–intein antimicrobials can selectively target and kill antibiotic-resistant bacteria in mixed populations
Autor/es | López Igual, Rocío
Bernal Bayard, Joaquín Rodríguez Patón, Alfonso Ghigo, Jean Marc Mazel, Didier |
Departamento | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2019 |
Fecha de depósito | 2023-02-13 |
Publicado en |
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Resumen | Targeted killing of pathogenic bacteria without harming beneficial members of host microbiota holds promise as a strategy to cure disease and limit both antimicrobial-related dysbiosis and development of antimicrobial ... Targeted killing of pathogenic bacteria without harming beneficial members of host microbiota holds promise as a strategy to cure disease and limit both antimicrobial-related dysbiosis and development of antimicrobial resistance. We engineer toxins that are split by inteins and deliver them by conjugation into a mixed population of bacteria. Our toxin–intein antimicrobial is only activated in bacteria that harbor specific transcription factors. We apply our antimicrobial to specifically target and kill antibiotic-resistant Vibrio cholerae present in mixed populations. We find that 100% of antibiotic-resistant V. cholerae receiving the plasmid are killed. Escape mutants were extremely rare (10−6–10−8). We show that conjugation and specific killing of targeted bacteria occurs in the microbiota of zebrafish and crustacean larvae, which are natural hosts for Vibrio spp. Toxins split with inteins could form the basis of precision antimicrobials to target pathogens that are antibiotic resistant. |
Agencias financiadoras | Centre national de la recherche scientifique (CNRS). France French Government Investissement d'Avenir. France Agencia Estatal de Investigación. España Comunidad Autónoma de Madrid Fondation pour la Recherche Médicale. France |
Identificador del proyecto | CNRS-UMR 3525
ANR-10-LABX-62-IBEID TIN2016-81079-R B2017/BMD-3691 DBF20160635736 DEQ20140329508 |
Cita | López Igual, R., Bernal Bayard, J., Rodríguez Patón, A., Ghigo, J.M. y Mazel, D. (2019). Engineered toxin–intein antimicrobials can selectively target and kill antibiotic-resistant bacteria in mixed populations. Nature Biotechnology, 37 (7), 755-760. https://doi.org/10.1038/s41587-019-0105-3. |
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