Article
Engineered toxin–intein antimicrobials can selectively target and kill antibiotic-resistant bacteria in mixed populations
Author/s | López Igual, Rocío
![]() ![]() ![]() ![]() ![]() ![]() ![]() Bernal Bayard, Joaquín ![]() ![]() ![]() ![]() ![]() ![]() ![]() Rodríguez Patón, Alfonso Ghigo, Jean Marc Mazel, Didier |
Department | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular Universidad de Sevilla. Departamento de Genética |
Publication Date | 2019 |
Deposit Date | 2023-02-13 |
Published in |
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Abstract | 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. |
Funding agencies | 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 |
Project ID. | CNRS-UMR 3525
![]() ANR-10-LABX-62-IBEID ![]() TIN2016-81079-R ![]() B2017/BMD-3691 ![]() DBF20160635736 ![]() DEQ20140329508 ![]() |
Citation | 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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