Lesley is involved in all aspects of the characterisation of type II topoisomerases, in particular DNA gyrase and DNA topoisomerase IV, which are essential to bacterial cells.
Humans do not possess these enzymes which make them very attractive drug targets.
In the light of increasing antimicrobial resistance, there is an urgent need for new compounds with novel modes of action to be found. Furthering our knowledge of the way topoisomerases work in general, can lead to better understanding of how resistance arises and to better evaluate any new compounds that may act as inhibitors of these enzymes, which in turn may lead to new antibiotic discovery.
Lesley often initiates projects, will train and supervise other workers in the group and is responsible for the day to day running of the lab. Currently, Lesley is working specifically on compounds that inhibit E. coli topo IV and is also involved in creating a comprehensive E. coli gyrase BA fusion mutant library for future screening against gyrase inhibitors.
Stracy M., Wollman A. J. M., Kaja E., Gapinski J., Lee J. E., Leek V. A., McKie S. J., Mitchenall L. A., Maxwell A., Sherratt D. J., Leake M. C., Zawadzki P. (2019)Single-molecule imaging of DNA gyrase activity in living Escherichia coli.Nucleic acids research (47)Publisher's version: 0305-1048
Mitchenall L. A., Hipkin R. E., Piperakis M. M., Burton N. P., Maxwell A. (2018)A rapid high-resolution method for resolving DNA topoisomers.BMC Research Notes (11)Publisher's version: 1756-0500
Colgan A. M., Quinn H. J., Kary S. C., Mitchenall L. A., Maxwell A., Cameron A. D. S., Dorman C. J. .. (2018)Negative supercoiling of DNA by gyrase is inhibited in Salmonella enterica serovar Typhimurium during adaptation to acid stress.Molecular Microbiology (107)Publisher's version: 0950-382X