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.

中文翻译：

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金叶酸类药物作为潜在的抗结核药物


结核分枝杆菌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。对现有药物进行测试以发现对分枝杆菌具有活性的药物可能是一个不错的选择。在这项工作中，金黄色酸组的抗生素在模型生物耻垢分枝杆菌上进行了测试。我们推测该组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，并揭示了治疗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MSMEG_3743/soj和MSMEG_4228/ftsW表达增加。因此，药物可能会影响细胞分裂，可能破坏 Z 环的功能和隔膜的形成。此外，几个不可或缺的基因的转录水平下降，例如硝酸还原酶亚基（ MSMEG_5137/narI和MSMEG_5139/narX ）和MSMEG_3205/hisD 。我们得出结论，金黄色酸及其相关化合物的作用机制可能与贝达喹啉类似，会扰乱细胞内的NAD+/NADH平衡。所有这些使我们得出结论，金黄色酸衍生物可以被视为潜在的抗结核药物。