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Nature communications
Jul 27, 2024;15 (1): 6332.

A bacteriocin expression platform for targeting pathogenic bacterial species.

Jack W Rutter, Linda Dekker, Chania Clare, Zoe F Slendebroek, Kimberley A Owen, Julie A K McDonald, Sean P Nair, Alex J H Fedorec, Chris P Barnes
Author Information
  1. Jack W Rutter: Department of Cell and Developmental Biology, University College London, London, UK. ORCID
  2. Linda Dekker: Department of Cell and Developmental Biology, University College London, London, UK. ORCID
  3. Chania Clare: Department of Cell and Developmental Biology, University College London, London, UK. ORCID
  4. Zoe F Slendebroek: Department of Cell and Developmental Biology, University College London, London, UK.
  5. Kimberley A Owen: Department of Cell and Developmental Biology, University College London, London, UK. ORCID
  6. Julie A K McDonald: Centre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College London, London, UK.
  7. Sean P Nair: Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, UK. ORCID
  8. Alex J H Fedorec: Department of Cell and Developmental Biology, University College London, London, UK. ORCID
  9. Chris P Barnes: Department of Cell and Developmental Biology, University College London, London, UK. christopher.barnes@ucl.ac.uk. ORCID
PMID: 39068147 DOI: 10.1038/s41467-024-50591-8

Abstract

Bacteriocins are antimicrobial peptides that are naturally produced by many bacteria. They hold great potential in the fight against antibiotic resistant bacteria, including ESKAPE pathogens. Engineered live biotherapeutic products (eLBPs) that secrete bacteriocins can be created to deliver targeted bacteriocin production. Here we develop a modular bacteriocin secretion platform that can be used to express and secrete multiple bacteriocins from non-pathogenic Escherichia coli host strains. As a proof of concept we create Enterocin A (EntA) and Enterocin B (EntB) secreting strains that show strong antimicrobial activity against Enterococcus faecalis and Enterococcus faecium in vitro, and characterise this activity in both solid culture and liquid co-culture. We then develop a Lotka-Volterra model that can be used to capture the interactions of these competitor strains. We show that simultaneous exposure to EntA and EntB can delay Enterococcus growth. Our system has the potential to be used as an eLBP to secrete additional bacteriocins for the targeted killing of pathogenic bacteria.

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Grants

  1. EP/W004674/1/RCUK | Engineering and Physical Sciences Research Council (EPSRC)
  2. EP/X026892/1/RCUK | Engineering and Physical Sciences Research Council (EPSRC)
  3. EP/W004674/1/RCUK | Engineering and Physical Sciences Research Council (EPSRC)
  4. EP/W004674/1/RCUK | Engineering and Physical Sciences Research Council (EPSRC)
  5. MR/W025655/1/RCUK | Medical Research Council (MRC)

MeSH Term

Bacteriocins
Enterococcus faecalis
Enterococcus faecium
Escherichia coli
Anti-Bacterial Agents
Microbial Sensitivity Tests
Coculture Techniques

Chemicals

Bacteriocins
Anti-Bacterial Agents
enterocin A
enterocin B
Journal Article
Article has an altmetric score of 11

Word Cloud

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