Validation of Innovative Lipopeptide Antibiotics

ended

Antibiotic resistance presents a growing threat to global health. The emergence of the superbugs is alarming: at current rates of increase, and without new intervention strategies, antibiotic resistance could cause a staggering 10 million deaths/year worldwide by 2050. Therefore, new approaches need to be developed to combat antibiotic resistance, particularly for the WHO’s priority pathogens which include the so-called ESKAPE family of dangerous drug-resistant bacteria. Recently, we developed a novel technology platform comprising a set of methodologies to semisynthetically modify the natural antibiotic nisin. In doing so we generated novel lipopeptide antibiotics with a much higher in vivo stability than the parent compound. These semisynthetic antibiotics possess a lipid II-mediated mode of action similar to nisin, which sets them apart from any current clinically-used antibiotic. During my ERC CoG, we have significantly improved these compounds, i.e. increased their antimicrobial activity and eliminated undesired haemolytic effects. Importantly, preliminary data shows that these antibiotics have a lower propensity to lose their potency due to antibiotic resistance development. I propose that these innovative lipopeptide antibiotics present a significant step forward in addressing the alarming threat of antibiotic resistance. However, to establish their commercial viability and broad applicability, the efficacy and preliminary safety of the new compounds need to be addressed. This can best be achieved via a PK/PD proof of concept study in appropriate animal models along with with a detailed evaluation of the business opportunity. The main objective of VOILA is therefore to establish both the technical feasibility and commercial viability of an entirely new class of lipopeptide antibiotics that is enabled by our innovative technology platform.