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 and Chris P. Barnes ()
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Jack W. Rutter: University College London
Linda Dekker: University College London
Chania Clare: University College London
Zoe F. Slendebroek: University College London
Kimberley A. Owen: University College London
Julie A. K. McDonald: Department of Life Sciences, Imperial College London
Sean P. Nair: UCL Eastman Dental Institute, University College London
Alex J. H. Fedorec: University College London
Chris P. Barnes: University College London

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50591-8

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