Abstract:
Mycobacterium tuberculosis is one of the most dangerous pathogens. Bacterial resistance to
antituberculosis drugs grows each year, but searching for new drugs is a long process. Testing for
available drugs to find active against mycobacteria may be a good alternative. In this work,
antibiotics of the aureolic acid group were tested on a model organism Mycobacterium smegmatis.
We presumed that antibiotics of this group may be potential G4 ligands. However, this was not
confirmed in our analyses. We determined the antimicrobial activity of these drugs and revealed
morphological changes in the cell structure upon treatment. Transcriptomic analysis documented
increased expression of MSMEG_3743/soj and MSMEG_4228/ftsW, involved in cell division. Therefore,
drugs may affect cell division, possibly disrupting the function of the Z-ring and the formation of a
septum. Additionally, a decrease in the transcription level of several indispensable genes, such as
nitrate reductase subunits (MSMEG_5137/narI and MSMEG_5139/narX) and MSMEG_3205/hisD was
shown. We concluded that the mechanism of action of aureolic acid and its related compounds may
be similar to that bedaquiline and disturb the NAD+/NADH balance in the cell. All of this allowed
us to conclude that aureolic acid derivatives can be considered as potential antituberculosis drugs.
