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

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 conju... Full description

Journal Title: Nature biotechnology 2019-07, Vol.37 (7), p.755-760
Main Author: López-Igual, Rocío
Other Authors: Bernal-Bayard, Joaquín , Rodríguez-Patón, Alfonso , Ghigo, Jean-Marc , Mazel, Didier
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1087-0156
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recordid: cdi_hal_primary_oai_HAL_pasteur_02558499v1
title: Engineered toxin–intein antimicrobials can selectively target and kill antibiotic-resistant bacteria in mixed populations
format: Article
creator:
  • López-Igual, Rocío
  • Bernal-Bayard, Joaquín
  • Rodríguez-Patón, Alfonso
  • Ghigo, Jean-Marc
  • Mazel, Didier
subjects:
  • Animals
  • Anti
  • Anti-Bacterial Agents - chemistry
  • Anti-Bacterial Agents - pharmacology
  • Anti-infective agents
  • Antibiotic resistance
  • Antibiotics
  • Antiinfectives and antibacterials
  • Antimicrobial agents
  • Antimicrobial resistance
  • Antitoxin Systems
  • Artemia
  • Artemia - microbiology
  • Bacteria
  • Bacterial Agents
  • Bacterial Toxins
  • Bacterial Toxins - pharmacology
  • Biotechnology
  • chemistry
  • Conjugation
  • Crustaceans
  • Disease control
  • Dosage and administration
  • drug effects
  • Drug resistance
  • Dysbacteriosis
  • Genetic Engineering
  • Inteins
  • Larva
  • Larva - microbiology
  • Larvae
  • Life Sciences
  • Microbiology
  • Microbiology and Parasitology
  • Microbiota
  • Molecular biology
  • Mutants
  • Parasitology
  • Patient outcomes
  • pharmacology
  • Plasmids
  • Populations
  • Toxin
  • Toxin-Antitoxin Systems
  • Toxins
  • Transcription factors
  • Vibrio cholerae
  • Vibrio cholerae - drug effects
  • Waterborne diseases
  • Zebrafish
  • Zebrafish - microbiology
ispartof: Nature biotechnology, 2019-07, Vol.37 (7), p.755-760
description: 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.
language: eng
source:
identifier: ISSN: 1087-0156
fulltext: no_fulltext
issn:
  • 1087-0156
  • 1546-1696
url: Link


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titleEngineered toxin–intein antimicrobials can selectively target and kill antibiotic-resistant bacteria in mixed populations
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descriptionTargeted 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.
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languageeng
publisherUnited States: Nature Publishing Group
subjectAnimals ; Anti ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Anti-infective agents ; Antibiotic resistance ; Antibiotics ; Antiinfectives and antibacterials ; Antimicrobial agents ; Antimicrobial resistance ; Antitoxin Systems ; Artemia ; Artemia - microbiology ; Bacteria ; Bacterial Agents ; Bacterial Toxins ; Bacterial Toxins - pharmacology ; Biotechnology ; chemistry ; Conjugation ; Crustaceans ; Disease control ; Dosage and administration ; drug effects ; Drug resistance ; Dysbacteriosis ; Genetic Engineering ; Inteins ; Larva ; Larva - microbiology ; Larvae ; Life Sciences ; Microbiology ; Microbiology and Parasitology ; Microbiota ; Molecular biology ; Mutants ; Parasitology ; Patient outcomes ; pharmacology ; Plasmids ; Populations ; Toxin ; Toxin-Antitoxin Systems ; Toxins ; Transcription factors ; Vibrio cholerae ; Vibrio cholerae - drug effects ; Waterborne diseases ; Zebrafish ; Zebrafish - microbiology
ispartofNature biotechnology, 2019-07, Vol.37 (7), p.755-760
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descriptionTargeted 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.
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42Toxin
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45Transcription factors
46Vibrio cholerae
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abstractTargeted 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.
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