Aureolic Acid Group of Agents as Potential Antituberculosis Drugs

Antibiotics

Ksenia Klimina¹  Galina Pozmogova¹  Egor Shitikov¹  Elena Ilina¹  Dmitry Bespiatykh¹  Tatiana Nikolenko¹  Maja Malakhova¹  Julia Bespyatykh¹  Anna Varizhuk¹  Anna Tevyashova²  Andrey Bespyatykh³ 

[1] Federal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, Russia;Gause Institute of New Antibiotics, 199021 Moscow, Russia;Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia;

关键词: Mycobacterium smegmatis;    TB treatment;    Olivomycin;    Mycobacterium tuberculosis;    transcriptomic;   

DOI  :  10.3390/antibiotics9100715

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown