Antibacterial Short Peptides Mediated by Toxin/Anti-toxin Mechanism

Peptide-Based Induction of Bacterial Cell Death

The Application

• The bacterial toxin MazF induces bacterial cell death by triggering downstream death pathways. The labile anti-toxin MazE is constantly synthesized by bacteria and inactivates MazF by sequestering it.
• Several antibiotics, such as rifampicin, chloramphenicol, mitomycin C act by affecting the MazF/MazE balance.

Innovation Highlights

• The invention is based on the recently discovered Extracellular Death Factor (EDF). EDF is a secreted bacterial pentapeptide which induces MazF-mediated cell death. EDF is the only naturally-occurring peptide known to act as a ‘quorum sensing' DEATH factor.
• EDF target bacteria includes different E.coli strains. Staphylicoccus aureus, Psedomonas aeruginosa, and Bacillus subtilis EDF-like factors are under current research. 
• The innovation concerns also EDF antagonists, which may confer antibiotic sensitivity by inducing mazEF plasmid loss.
• EDF-based antibacterial composition may be used for sterilizing as well as for pharmaceutical purposes.
• Possibility of modifying the EDF original sequence by the addition of amino acids and other moieties, thus improving physiological properties and allowing different administration modes.

Current Development Stage

Proof of concept established in different E.coli strains.

The Opportunity

• The list of conditions induced by potentially EDF-targeted bacteria includes: diarrhea, dysentery, hemorrhagic colitis, pyogenic infection, abscesses, septicaemia, pneumonia, meningitis, lung infection, cystic fibrosis.
• EDF-based compounds provide a new and specific venue to induce bacterial cell death.

Patent Status

Granted US 9,012,152