Bespyatykh Julia, Bespiatykh Dmitry, Malakhova Maja, Klimina Ksenia, Bespyatykh Andrey, Varizhuk Anna, Tevyashova Anna, Nikolenko Tatiana, Pozmogova Galina, Ilina Elena, Shitikov Egor
Federal Research and Clinical Centre of Physical-Chemical Medicine, 119435 Moscow, Russia.
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Antibiotics (Basel). 2020 Oct 19;9(10):715. doi: 10.3390/antibiotics9100715.
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 . 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 and , 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 ( and ) and 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.
是最危险的病原体之一。细菌对抗结核药物的耐药性逐年增加，但寻找新药是一个漫长的过程。测试现有药物以发现对分枝杆菌有活性的药物可能是一个不错的选择。在这项工作中，对金霉素类抗生素在一种模式生物上进行了测试。我们推测该类抗生素可能是潜在的G4配体。然而，我们的分析并未证实这一点。我们确定了这些药物的抗菌活性，并揭示了处理后细胞结构的形态变化。转录组分析记录了参与细胞分裂的和的表达增加。因此，药物可能影响细胞分裂，可能破坏Z环的功能和隔膜的形成。此外，还显示了几个不可或缺的基因转录水平的降低，如硝酸还原酶亚基（和）以及。我们得出结论，金霉素及其相关化合物的作用机制可能与贝达喹啉相似，并扰乱细胞中的NAD+/NADH平衡。所有这些使我们能够得出结论，金霉素衍生物可被视为潜在的抗结核药物。
