The Foundation for Medical Research, 84-A, R.G. Thadani Marg, Worli, Mumbai, 400 018, India.
Molecular Virology Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Powai, Mumbai, 400076, India.
Curr Microbiol. 2018 Apr;75(4):394-400. doi: 10.1007/s00284-017-1393-9. Epub 2017 Nov 16.
Alternate mechanisms of drug resistance involving intrinsic defense pathways play an important role in development of drug resistance. Deregulation of drug efflux, cellular metabolism, and DNA repair have been indicated to have effect on drug tolerance and persistence. Here we chose eight genes from these pathways to investigate their association with development of multidrug resistance (MDR). We generated mono drug resistant and MDR strains of rifampicin and isoniazid and examined the differential expression of genes belonging to efflux, DNA repair and cell wall lipid synthesis pathways. Rv1687c, recB, ppsD and embC genes showed significant (P <0.05) upregulation in mono-resistant (both rifampicin and isoniazid) as well as MDR strains. mmr showed significant upregulation with rifampicin resistance while Rv1457c showed significant upregulation only with mono-resistant strains. Highest expression change was observed with Rv1687c and ppsD. The study identified potential key genes that are significantly associated with development of drug resistance in vitro. These genes may help identify clinical strains predisposed to acquiring drug resistance in patients during the course of treatment or help in management of MDR forms of tuberculosis.
涉及固有防御途径的耐药性的替代机制在耐药性的发展中起着重要作用。药物外排、细胞代谢和 DNA 修复的失调被表明对药物耐受性和持久性有影响。在这里，我们选择了这些途径中的 8 个基因来研究它们与多药耐药（MDR）发展的关系。我们生成了利福平和异烟肼的单药耐药和 MDR 菌株，并检测了属于外排、DNA 修复和细胞壁脂质合成途径的基因的差异表达。Rv1687c、recB、ppsD 和 embC 基因在单耐药（利福平和异烟肼）以及 MDR 菌株中均显著上调（P<0.05）。mmr 与利福平耐药性显著上调，而 Rv1457c 仅在单耐药菌株中显著上调。Rv1687c 和 ppsD 的表达变化最大。该研究确定了与体外耐药性发展显著相关的潜在关键基因。这些基因可能有助于识别在治疗过程中患者易发生耐药性的临床菌株，或有助于管理 MDR 形式的结核病。
