Structure determination of new complexes for DNA Gyrase from Mycobacterium tuberculosis

Fluoroquinolones, particularly Moxifloxacin (MFX) and Levofloxacin (LFX) have been
gaining prominence in the context of tuberculosis treatment [1] and their use has been
recently recommended by WHO [2]. This class of drugs acts upon bacterial type II and IV
topoisomerases and DNA Gyrase [3]. Nevertheless, differently than other bacterial species,
Mycobacterium tuberculosis (MTB) does not possess type IV topoisomerases, and only
DNA gyrase, a type II topoisomerase. Since fluoroquinolones are already part of the
current treatment regimens established for MTB infection, being the most prominent
second-line drug used, many fluoroquinolones resistant MTB strains have already been
reported in the literature. Therefore, there is an urgent need to identify and validate novel
molecules that can target DNA gyrase interacting in novel binding sites, in order to have
more therapeutic options in cases of resistance, or help shorten the current treatment
regimen for tuberculosis.