Tuberculosis drug resistance (DR) is a global problem that is not fully elucidated. Previously, overexpression of esxG and esxH genes was reported in a multidrug-resistant (MDR) Mycobacterium tuberculosis isolate compared with a reference H37Rv strain. To evaluate the roles of esxG and esxH in DR, analysis of their regulatory and coding sequences in sensitive and resistant strains was performed, and the expression levels of their transcriptional regulators IdeR, Zur, and MntR were evaluated. esxG and esxH were expressed heterologously using mycobacterial constructs, and the orthologs Msmeg_0620 and Msmeg_0621 were attenuated in Mycobacterium smegmatis by antisense knockdown. We found no differences in the regulatory and coding sequences of esxG and esxH between the sensitive strain and the MDR isolate. Expression analysis of transcriptional regulators showed that ideR was upregulated in isoniazid (INH)-resistant isolates; in addition, growth inhibition of the M. smegmatis strain was observed in the presence of rifampicin (RIF) and INH when esxG and esxH were expressed heterologously, while faster growth in the presence of RIF was observed when the orthologs were attenuated. In conclusion, the expression of esxG and esxH altered the growth of Mycobacterium in the presence of INH and RIF, suggesting a potential association with DR.

中文翻译：

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esxG 和 esxH 基因在耐药分枝杆菌中的作用。

结核病耐药性 (DR) 是一个尚未完全阐明的全球性问题。以前，与参考 H37Rv 菌株相比，多药耐药 (MDR)结核分枝杆菌分离株中报告了esxG和esxH基因的过度表达。为了评估esxG和esxH在 DR 中的作用，对它们在敏感和抗性菌株中的调节和编码序列进行了分析，并评估了它们的转录调节因子 IdeR、Zur 和 MntR 的表达水平。esxG和esxH使用分枝杆菌构建体异源表达，直系同源物Msmeg_0620和Msmeg_0621通过反义敲低在耻垢分枝杆菌中减毒。我们发现敏感菌株和 MDR 分离株之间esxG和esxH的调控和编码序列没有差异。转录调控因子的表达分析表明，ideR在异烟肼 (INH) 抗性分离株中上调；此外，当esxG和esxH异源表达时，在利福平 (RIF) 和 INH 的存在下观察到耻垢分枝杆菌菌株的生长抑制，而当直向同源物减毒时，在 RIF 存在下观察到更快的生长。综上所述，esxG和esxH的表达在 INH 和 RIF 存在下改变分枝杆菌的生长，表明与 DR 的潜在关联。