URSs peptides may enable the development of a method to overcome inevitable resistance
2Faculty of Biotechnology and Food Engineering, Technion – Israel Institute of Technology, Haifa Israel 32000.
In a study previously published by our laboratory (Navon et al. PNAS 2016), we scanned the proteome databases of a variety of pathogenic bacterial species using an in-house computer program that detects short (3-4 amino acids), linear amino acid sequences which are significantly under-represented (URSs). We showed that different bacteria have different URSs, which in some cases are completely absent from a proteome. We proposed that these sequences are absent due to a deleterious effect in cell viability. We showed experimentally that this is indeed the case due to translation inhibition, when proteins with an embedded URS are expressed in E. coli, in vivo, in vitro or by single molecule translation assays. The human proteome does not lack any unique sequence of three-amino acids.
We now show that Incubation of bacterial cells with synthetic peptides containing the URSs is bactericidal. Since these bacterial URSs are not missing from the human proteome, we assume that these peptides may be used as a novel type of antibiotics. Our recent determination of the three dimensional structures of ribosomes with bound URS peptides is described in the abstract submitted by Tarabeh et al.
We will describe here that latest results of experiments aimed at better understanding the physicochemical characteristics of the URS peptides with respect to efficacy (MIC), cellular penetration, peptide stability and resistance prevention. We propose that the existence of multiple URSs may enable the development of a method to overcome inevitable resistance.