Being among the most significant challenges facing modern medicine, the massive growth of multi-drug resistance prolongs illnesses and increases the risk of early death, thus creating a global clinical threat. The limited arsenal of available antibiotics dictates an urgent need for novel approaches, as it suffers from (i) resistance to one or several antibiotics and (ii) marginal distinction between the antibiotics sites in bacteria and in patients, causing toxicity or side effects. As resistance-acquiring mechanisms are species-specific and as many antibiotics target ribosomes, we developed novel methodologies for increasing the battery of available potent antibiotics by benefiting from the breakthroughs of our NOVRIB ERC funded project: the unexpected rapid determination of the only available high resolution structure of a ribosome from a genuine pathogen, worldwide.
In this PoC project we propose to exploit the unique tools provided by this structure for the commercialization of newly discovered binding sites and contact-networks, for suggesting novel synthetic antibiotics and/or for structure-based alterations of existing ones. Thus, we identified chemical elements associated solely with pathogenic specificity that can provide valuable clues for designing modifications that should increase the potency of the currently known antibiotics; alongside proposing novel binding sites on the ribosome surface. The advantages of our approach are (1) less chance of fast developing resistance, (2) reduced toxicity, (3) potential of decelerating multi-drug antimicrobial resistance development, (4) improved existing ribosomal antibiotics. The significance of our innovating approach stems also from the potential market and the compelling socioeconomic benefits. Hence, we are currently approaching the stage of commercialization and public dissemination.
Fields of science
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