A new class of antibiotics

Resistance to antimicrobial agents is a growing global issue requiring new compounds to enter the market. Very few novel agents have been developed recently. Moreover, most antibiotics under clinical investigation belong to existing families of compounds that will most likely be subjected to the same mechanisms of resistance.

To address this, the EU-funded NABARSI (New antibacterials with inhibitory activity on aminoacyl-tRNA synthetases) project will undertake cutting-edge drug discovery activities to identify new chemical entities that could serve as antimicrobial agents. Activities to be performed include cheminformatics and bioinformatics analysis, new chemical entity synthesis, the development of primary screening assays, ADME studies and the testing of suitable NCEs in animal models of infection. New chemical entities will be tested against multi-antibiotic resistant pathogenic ‘ESKAPE’ bacteria i.e. Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species and Escherichia coli.

NABARSI research will focus on potential inhibitors of aminoacyl-tRNA synthetases (aaRS) - enzymes required for bacterial protein synthesis - and drug design will be based on in silico research of a database of nearly 8 million chemical compounds.

Considerable effort will be placed into the development of assays for assessing enzymatic activity and testing bacterial susceptibility to the newly designed chemical entities. Using these new chemical structures the consortium will attempt to improve compound design to achieve maximum bacterial growth inhibition, whilst specifically targeting bacterial aaRS activity.

Overall, the aim of the NABARSI project is to identify a potentially new antibiotic that may be used to treat patients infected with multi-antibiotic resistant bacterial pathogens. If successful, the NABARSI-developed antibiotic could help significantly reduce the socioeconomic burden associated with multi-antibiotic resistant bacterial infections.