Previous studies have reported that genome-wide DNA methylation and differentially expressed genes and proteins are closely associated with drug resistance in Mycobacterium tuberculosis (M. tuberculosis). However, no reports have explored such associations in para-aminosalicylic acid (PAS)-resistant M. tuberculosis H37Rv. Here, we investigated genome-wide methylation and transcriptome and proteome changes to explore the associations between specific genes and PAS resistance in M. tuberculosis H37Rv. The results revealed that 1,388 differentially methylated (1,161 hypermethylated and 227 hypomethylated) genes, 214 significantly differentially expressed (103 up- and 111 down-regulated) genes and 137 differentially expressed (48 up- and 89 down-regulated) proteins were regulated by PAS in M. tuberculosis H37Rv. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that metabolic pathways and ABC transporters were closely associated with differentially methylated and expressed genes, respectively. In addition, correlation analysis revealed that differentially methylated genes were negatively correlated with their transcriptional levels in PAS-resistant M. tuberculosis H37Rv. Furthermore, the existence of five hypermethylated candidate genes (esxC, fabG3, fbpB, papA1 and pks2) in PAS-resistant M. tuberculosis H37Rv was verified using protein-protein interaction analysis in the STRING database. The integrated DNA methylation and transcriptome and proteome analysis could provide valuable resources for epigenetics studies in PAS-resistant M. tuberculosis H37Rv.

中文翻译：

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具有对氨基水杨酸抗性的结核分枝杆菌中全基因组DNA甲基化以及转录组和蛋白质组的变化。

先前的研究报道，全基因组DNA甲基化以及差异表达的基因和蛋白质与结核分枝杆菌（M. tuberculosis）的耐药性密切相关。但是，尚无报道探讨对氨基水杨酸（PAS）耐药结核分枝杆菌H37Rv中的这种关联。在这里，我们调查了全基因组甲基化以及转录组和蛋白质组的变化，以探索结核分枝杆菌H37Rv中特定基因与PAS抗性之间的关联。结果显示，PAS调节了1,388个差异甲基化的基因（1,161个高甲基化和227个低甲基化的基因），214个显着差异表达（103个上调和111个下调）基因和137个差异表达（48个上调和89个下调）蛋白。在结核分枝杆菌H37Rv中。京都基因与基因组百科全书（KEGG）途径分析显示，代谢途径和ABC转运蛋白分别与差异甲基化和表达的基因密切相关。另外，相关分析显示，在耐PAS的结核分枝杆菌H37Rv中，差异甲基化基因与其转录水平呈负相关。此外，使用STRING数据库中的蛋白质-蛋白质相互作用分析，证实了PAS耐药结核分枝杆菌H37Rv中存在五个高甲基化候选基因（esxC，fabG3，fbpB，papA1和pks2）。整合的DNA甲基化，转录组和蛋白质组分析可以为抗PAS的结核分枝杆菌H37Rv的表观遗传学研究提供有价值的资源。