Details

Autor(en) / Beteiligte

• López-Igual, Rocío
• Bernal-Bayard, Joaquín
• Rodríguez-Patón, Alfonso
• Ghigo, Jean-Marc
• Mazel, Didier

Titel

Engineered toxin-intein antimicrobials can selectively target and kill antibiotic-resistant bacteria in mixed populations

Ist Teil von

• Nature biotechnology, 2019-07, Vol.37 (7), p.755-760

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Beschreibungen/Notizen

• 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 -10 ). 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.