Ghosh Arup, Biswas Viplov Kumar, Bal Himadri Bhusan, Das Dasarathi, Pati Sanghmitra, Gupta Bhawna, Raghav Sunil Kumar
Immunogenomics & Systems Biology group, Institute of Life Sciences (ILS), Bhubaneswar, Odisha, India; School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Bhubaneswar, Odisha, India.
ICMR-Regional Medical Research Centre, Bhubaneswar, India.
Infect Genet Evol. 2025 Mar;128:105713. doi: 10.1016/j.meegid.2025.105713. Epub 2025 Jan 11.
Whole genome sequencing has been used to investigate the genomic diversity of M. tuberculosis in the northern and southern states of India, but information about the eastern part of the country is still limited. Through a sequencing-based strategy, this study seeks to comprehend the diversity and drug resistance pattern in the eastern region. A total of 102 M. tuberculosis isolates from North East (n = 54), and Odisha (n = 48) were sequenced along with 7 follow up isolates from Sikkim. The pre-XDR and XDR isolates diagnosed as per the NTEP diagnostic algorithm were subjected for phenotypic second-line liquid culture drug susceptibility testing in MGIT-960 system. After filtering out low quality isolates based on taxonomic classification and depth of coverage, variant calling was performed. We observed a high prevalence of multi-drug resistant TB (MDR-TB) lineage 2 (52/54) isolates in northeast whereas there was a mixed representation of lineage 1 (30/48) & lineage 3 (11/48) in Odisha. The MDR-TB isolates from Sikkim posed a high rate (51/53) of fluoroquinolone resistance and pairwise SNV distances (≤10) indicating possible local transmission events in the region. We observed occurrence of genetic variations in genes associated with bedaquiline and delamanid resistance. Our findings show the diversity of M. tuberculosis vary across the eastern regions, in north eastern states lineage 2 has a dominant presence while lineage 1 and 3 has mixed representation in Odisha. The high prevalence of fluoroquinolone resistance in north eastern region associated with variations in gyrA gene and may have been caused by local transmission events based on genomic similarities.
全基因组测序已被用于研究印度北部和南部各邦结核分枝杆菌的基因组多样性，但该国东部地区的相关信息仍然有限。通过基于测序的策略，本研究旨在了解东部地区的多样性和耐药模式。对来自东北地区（n = 54）和奥里萨邦（n = 48）的总共102株结核分枝杆菌分离株以及来自锡金的7株后续分离株进行了测序。根据国家结核病消除计划（NTEP）诊断算法诊断出的预广泛耐药和广泛耐药分离株，在MGIT - 960系统中进行了表型二线液体培养药敏试验。在根据分类学分类和覆盖深度筛选出低质量分离株后，进行了变异检测。我们观察到东北地区多药耐药结核（MDR - TB）谱系2（52/54）分离株的高流行率，而在奥里萨邦，谱系1（30/48）和谱系3（11/48）呈现混合分布。来自锡金的MDR - TB分离株表现出高比例（51/53）的氟喹诺酮耐药性以及成对单核苷酸变异距离（≤10），表明该地区可能存在局部传播事件。我们观察到与贝达喹啉和地拉曼德耐药相关的基因发生了遗传变异。我们的研究结果表明，结核分枝杆菌的多样性在东部各地区有所不同，在东北地区谱系2占主导地位，而在奥里萨邦谱系1和3呈现混合分布。东北地区氟喹诺酮耐药的高流行率与gyrA基因变异有关，可能是基于基因组相似性的局部传播事件所致。
