1. A bacteriocin expression platform for targeting pathogenic bacterial species.
- Author
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Rutter JW, Dekker L, Clare C, Slendebroek ZF, Owen KA, McDonald JAK, Nair SP, Fedorec AJH, and Barnes CP
- Subjects
- Microbial Sensitivity Tests, Coculture Techniques, Bacteriocins pharmacology, Bacteriocins metabolism, Bacteriocins biosynthesis, Enterococcus faecalis metabolism, Enterococcus faecalis drug effects, Enterococcus faecalis genetics, Enterococcus faecium metabolism, Enterococcus faecium genetics, Enterococcus faecium drug effects, Escherichia coli metabolism, Escherichia coli drug effects, Escherichia coli genetics, Anti-Bacterial Agents pharmacology
- 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., (© 2024. The Author(s).)
- Published
- 2024
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