A novel strategy to target lethal peptides against antibiotic resistant bacteria

Extract: One of the major therapeutic challenges that face modern clinicians is the development of bacterial resistance to antibiotics. Currently, antibiotic resistance is a major problem in the treatment of staphylococcal, enterococcal, pneumocystis, helicobacter, and mycobacterial infections, to name a few. While there are several different mechanisms by which this occurs, the common pathway in the development of bacterial resistance has been the widespread use of broad-spectrum antibiotics as single agents. In the work summarized here, we devised a novel antibiotic, which could be used to overcome bacterial resistance to standard antibiotics. The concept is based on two principles. 1) Use of a toxin of bacterial origin, as a non-standard antibacterial mechanism of action. For this purpose, colicin Ia of E. coli, a peptide with channel forming properties, was selected in order to produce target cell rupture. 2) To target such a toxin to a particular bacterial organism, we took advantage of a natural mechanism used by these bacteria to communicate with each other, namely, the use of pheromones, which are bacterial peptides secreted and bound by membrane receptors in a species- and strain-specific manner.