The discovery of antibiotics has revolutionised medicine, allowing treatment of previously deadly infectious diseases but also allowing use of invasive techniques such as surgery.
However, antibiotic resistance threatens to nullify many of the medical advances made in the last 100 years. DNA gyrase is essential for the survival of bacteria.
It is a validated and effective target of many clinically used antibiotics including fluoroquinolones and aminocoumarins.
With the pressure of antimicrobial resistance ever increasing, it is imperative to identify new gyrase inhibitors with novel mechanisms of action. Microcin B17 (MccB17) is one such inhibitor. It is a microbial toxin produced by Escherichia coli strains possessing the MccB17 plasmid.
The 3 kDa post-translationally modified peptide targets DNA gyrase, however, despite understanding its structure, its mechanism of action remains an enigma.
Rebecca aims to develop a universal tool to study gyrase inhibitors through generating a library of gyrase mutants.
These mutant gyrase species can then be assayed with MccB17 or other inhibitors to identify resistant species and hence identify binding sites.
Farrell L. J., Lo R., Wanford J. J., Jenkins A., Maxwell A., Piddock L. J. V. (2018)Revitalizing the drug pipeline: AntibioticDB, an open access database to aid antibacterial research and development.The Journal of antimicrobial chemotherapy (73)Publisher's version: 0305-7453