Peptoids as antibacterial agents promoting MazF toxin activity in E. coli
Toxin-antitoxin systems are diverse genetic modules ubiquitous in bacteria. They express a toxin, disruptive to its parent cell, and an antitoxin, which abrogates the corresponding toxin’s activity. Factors like environmental stress can disrupt the toxin-antitoxin equilibrium, allowing the toxin to exert its lethal effect. MazE-MazF proteins form one of such systems present in gram-negative bacteria. MazF toxin is active when not bound to MazE, causing several abnormalities and ultimately death of affected bacterial cells. Specific peptides, known as Extracellular Death Factors (EDFs), can also promote MazF activity. However, practical use of EDFs in combating bacterial infections is precluded by their low efficacy and susceptibility to proteolysis. Replacing peptides with peptidomimetics, e.g., peptoids, can address these issues. Peptoids differ from peptides in the attachment point of their sidechains, altering their properties and providing high resistance to enzymatic proteolysis.
The aim of the project is to test peptoid analogs of EDFs as effective agents promoting MazF toxin activity. This goal is accompanied by the optimization of peptoid synthesis protocols, which will be applicable to other projects involving peptoids and peptide-peptoid hybrids.
Principal Investigator: dr Piotr Maj
Project period: 2024 – 2025
Funding: Miniatura 8, National Science Centre
