通过全基因组测序揭示结核分枝杆菌药物敏感和耐药分离株的新突变和遗传变异：来自印度北方邦东部的一项研究

IF 1.4 4区医学 Q4 IMMUNOLOGY

Indian Journal of Medical Microbiology Pub Date : 2025-06-11 DOI:10.1016/j.ijmmb.2025.100895

Kamal Singh , Saravanan Vijayakumar , Swati Sharma , Shampa Anupurba

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引用次数: 0

摘要

目的耐药结核病（DR-TB）是全球公共卫生面临的一个巨大挑战。因此，本研究旨在利用全基因组测序技术（WGS）阐明药敏（DS）和耐药结核分离株的完整遗传谱。方法收集不同个体的5例DS-TB、MDR-TB和广泛耐药结核病（XDR-TB）痰标本。采用GeneXpert法、基因型mmtdr +法和基因型tbdrsl法进行鉴定和敏感性鉴定。此外，使用BD BACTEC MGIT 960培养标本，随后通过Capilia快速试剂盒进行确认。WGS用于鉴定单核苷酸多态性（snp），结核分枝杆菌复合体（MTBC）谱系和spoligotypes。H37Rv作为阳性对照。结果WGS结果显示，MDR-TB和XDR-TB分离株rpoB基因均出现Ser450Leu、Gln432Leu和His445Gln非同义突变。分离株同时携带fabG1-8T >突变；C、fabG1-17G >；T, fabG1-15C >；T和inh - 154g >；A. 1株DS-TB分离株在517C >位置携带rrs基因耐药突变；而三个耐多药结核分离株被证明是前广泛耐药结核，携带与氟喹诺酮（FQ）耐药相关的突变（gyrA Ala90Val、gyrA Asp94His和gyrA asp94gly）。本研究报道了MTBC临床分离株中新的突变pncA391dupG和thyX基因的首次突变。大多数耐多药/广泛耐药结核分离株主要与东亚2系中的北京亚系相关。总之，我们的研究突出了快速鉴定结核病菌株的挑战和有关结核病菌株遗传多样性的基本信息，这些信息为结核病流行病学提供了有价值的见解。

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Unearthing novel mutations and genetic variation in drug sensitive and resistant isolates of Mycobacterium tuberculosis through whole genome sequencing: A study from eastern Uttar Pradesh, India

Purpose

Drug-resistant tuberculosis (DR-TB) presents a formidable public health challenge worldwide. Therefore, this study was conducted to elucidate the complete genetic profiles of drug-sensitive (DS), and drug-resistant TB isolates using Whole Genome Sequencing (WGS).

Methods

The study includes a set of sputum specimens containing five DS-TB, multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) from distinct individuals. The identification and susceptibility was confirmed using GeneXpert assay, GenoType MTBDR plus assay, and GenoTypeMTBDRsl assay. Furthermore, specimens were cultured using the BD BACTEC MGIT 960 and subsequently confirmed through Capilia rapid kit. WGS was employed for the identification of Single Nucleotide Polymorphisms (SNPs), Mycobacterium tuberculosis complex (MTBC) lineages, and spoligotypes. The H37Rv was used as a positive control.

Results

The findings of WGS showed, all the MDR-TB and XDR-TB isolates exhibited non-synonymous mutation (Ser450Leu, Gln432Leu, and His445Gln) within the rpoB gene. The isolates were simultaneously harboring mutations at fabG1-8T > C, fabG1-17G > T, fabG1-15C > T, and inhA-154G > A. One DS-TB isolate was carrying resistance mutations in the rrs gene at position 517C > T, while three MDR-TB isolates turned out to be pre-XDR-TB carrying mutations associated with fluoroquinolone (FQ) resistance (gyrA Ala90Val, gyrA Asp94His, and gyrA Asp94 Gly). The study reports novel mutations pncA391dupG and for the first time mutation in thyX gene in clinical isolates of MTBC. Most of the MDR/XDR-TB isolates were predominantly associated with the Beijing sub-lineage within the East Asian Lineage 2.

Conclusions

In conclusion, our study highlighted the challenges surrounding the rapid identification and essential information regarding the genetic diversity of TB strains which contribute valuable insights into the TB epidemiology.

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来源期刊

Indian Journal of Medical Microbiology IMMUNOLOGY-

CiteScore

2.20

自引率

0.00%

发文量

154

审稿时长

73 days

期刊介绍： Manuscripts of high standard in the form of original research, multicentric studies, meta analysis, are accepted. Current reports can be submitted as brief communications. Case reports must include review of current literature, clinical details, outcome and follow up. Letters to the editor must be a comment on or pertain to a manuscript already published in the IJMM or in relation to preliminary communication of a larger study. Review articles, Special Articles or Guest Editorials are accepted on invitation.