Genome-wide analysis to detect multi-drug resistance genes in Mycobacterium tuberculosis strains SWLPK and MNPK resourced from Pakistan

M. Rafique, Muhammad Ibrahim, Sumaira Kanwal, H. Bokhari, F. Jamil, Annam Hussain, M. Rasheed
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Abstract

Development of multidrug-resistant tuberculosis is the after effect of various mutational occasions, which leads to the development of protection from hostile to multiple tuberculosis drugs. In this study, we identified drug resistance genes, their evolutionary analysis, mutational variation, and docking to characterize the drug target potentials of two Mycobacterium tuberculosis strains SWLPK and MNPK resourced from Pakistan. For this purpose, we used different bioinformatics tools including the RAST server for annotation, and UniProt, NCBI, BLAST and MUSCLE for data retrieval and analysis. Evolutionary relationships were drawn using MEGA 7. A 3D structure was modelled by I-TASSER, while refinement and minimizations were performed using the UCSF Chimera 1.14.1. Moreover, the Ramachandran plot was used to check the quality of the proteins, while PatchDock was used for the docking analysis. Based on the comparison with the reference genome (M. tuberculosis H37RV), the SWLPK and MNPK strains encoded 24 multi-drug resistance genes. The drug resistance genes of nearby strains had developmental relatedness and comparable useful attributes imperative to their ecological specialties. The docking analysis revealed that the proteins accurately bound at their binding region just like the reference protein H37Rv (NuoG). We identified 24 multi-drug resistance genes in the SWLPK and MNPK strains. Moreover, there were a few missing drug resistance genes found in H37Rv, which were not present in the MNPK and SWLPK strains. The 24 genes reported in the MNPK and SWLPK strains might have a major contribution in drug resistance.
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巴基斯坦结核分枝杆菌SWLPK和MNPK菌株多药耐药基因的全基因组分析
耐多药结核病的发展是多种突变事件的后果,导致了对多种结核病药物的保护发展。在这项研究中,我们鉴定了来自巴基斯坦的两株结核分枝杆菌SWLPK和MNPK的耐药基因,并对其进行了进化分析、突变变异和对接,以表征其药物靶标潜力。为此,我们使用了不同的生物信息学工具,包括RAST服务器进行注释,UniProt、NCBI、BLAST和MUSCLE进行数据检索和分析。利用mega7绘制了进化关系。三维结构采用I-TASSER建模,并用UCSF Chimera 1.14.1进行细化和最小化。此外,使用Ramachandran图检查蛋白质的质量,使用PatchDock进行对接分析。通过与参考基因组(结核分枝杆菌H37RV)的比较,SWLPK和MNPK菌株编码了24个多药耐药基因。邻近菌株的耐药基因具有发育亲缘性和可比性,这是其生态特性所必需的。对接分析显示,这些蛋白与参考蛋白H37Rv (NuoG)一样准确地结合在其结合区。我们在SWLPK和MNPK菌株中鉴定出24个多药耐药基因。此外,在H37Rv中发现了少量缺失的耐药基因,而这些基因在MNPK和SWLPK株中不存在。MNPK和SWLPK菌株中报道的24个基因可能对耐药起主要作用。
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