Advani Jayshree, Verma Renu, Chatterjee Oishi, Pachouri Praveen Kumar, Upadhyay Prashant, Singh Rajesh, Yadav Jitendra, Naaz Farah, Ravikumar Raju, Buggi Shashidhar, Suar Mrutyunjay, Gupta Umesh D, Pandey Akhilesh, Chauhan Devendra S, Tripathy Srikanth Prasad, Gowda Harsha, Prasad T S Keshava
Institute of Bioinformatics, International Technology Park, Bengaluru, India.
Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India.
Front Microbiol. 2019 Feb 26;10:309. doi: 10.3389/fmicb.2019.00309. eCollection 2019.
Whole genome sequencing (WGS) of has been constructive in understanding its evolution, genetic diversity and the mechanisms involved in drug resistance. A large number of sequencing efforts from across the globe have revealed genetic diversity among clinical isolates and the genetic determinants for their resistance to anti-tubercular drugs. Considering the high TB burden in India, the availability of WGS studies is limited. Here we present, WGS results of 200 clinical isolates of from North India which are categorized as sensitive to first-line drugs, mono-resistant, multi-drug resistant and pre-extensively drug resistant isolates. WGS revealed that 20% of the isolates were co-infected with and non-tuberculous mycobacteria species. We identified 12,802 novel genetic variations in isolates including 343 novel SNVs in 38 genes which are known to be associated with drug resistance and are not currently used in the diagnostic kits for detection of drug resistant TB. We also identified lineage 3 to be predominant in the northern region of India. Additionally, several novel SNVs, which may potentially confer drug resistance were found to be enriched in the drug resistant isolates sampled. This study highlights the significance of employing WGS in diagnosis and for monitoring further development of MDR-TB strains.
对[具体内容缺失]进行全基因组测序（WGS）有助于理解其进化、遗传多样性以及耐药机制。全球范围内大量的测序工作揭示了临床分离株之间的遗传多样性以及它们对抗结核药物耐药的遗传决定因素。鉴于印度结核病负担沉重，WGS研究的可得性有限。在此，我们展示了来自印度北部的200株[具体内容缺失]临床分离株的WGS结果，这些分离株被分类为对一线药物敏感、单耐药、多耐药和广泛耐药前的分离株。WGS显示20%的分离株与非结核分枝杆菌物种共同感染。我们在[具体内容缺失]分离株中鉴定出12,802个新的遗传变异，包括38个基因中的343个新的单核苷酸变异（SNV），这些基因已知与耐药性相关，且目前未用于耐药结核病检测的诊断试剂盒中。我们还发现3系在印度北部地区占主导地位。此外，在采集的耐药分离株中发现了几个可能潜在赋予耐药性的新SNV。这项研究突出了采用WGS进行诊断以及监测耐多药结核菌株进一步发展的重要性。
