Small transmembrane peptides for treatment of pathogenic bacteria.

The business concept of this project is the introduction of a new concept of antimicrobial treatment with a novel method of action to treat infectious diseases and the evolution of antibiotic resistance. The invention is a new class of small and extremely toxic peptides that rapidly kill the bacterial cell and increase the sensitivity of bacterium towards antibiotics and prevents antibiotic resistance. Anticipated results and objective for the proof of concept project. A highly successful outcome for thi s project would be to develop a helper phage system capable of packaging >90% of the bacteriophage particles with a phagemid containing a toxic transmembrane peptide. If this could be combined with the development of a bacterial strain resistant to the to xic effects of the peptide then efficiencies of production will be reached whereby we could carry out trials in vivo. Rigorous in vivo studies will greatly facilitate the establishment of links and financing from industry. An additional measure of high su ccess would be the ability to not only synthesis the toxic transmembrane peptide DinQ but also find a way to deliver the peptide and induce toxicity. This could be directly or via the attachment of moieties enable crossing of the outer membrane. Moderate success would be the successful mutagenesis of the helper phage system and to show a statistically improved packaging ratio. In addition, any increase to resistance to the toxins during production would also indicate moderate success together with the di scovery of any external conditions that help with production. A deeper understanding of the processes leading to cell death by DinQ single transmembrane peptides would also be considered, as this will increase our ability to rationally focus our work to e nhance toxicity during treatment. The synthesis of the DinQ peptide in itself would enable us to further examine how it exerts its toxic effect.