Classification of Mycobacterium tuberculosis DR, MDR,XDR Isolates and Identification of Signature MutationPattern of Drug Resistance

结核分枝杆菌耐药、多重耐药、广泛耐药菌株的分类及耐药特征突变模式的鉴定

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Abstract

Mycobacterium tuberculosis - a global threat, the recent breakout in MDR-TB and XDR-TB has challenged researchers in diagnosis to provide effective treatment. The main objective to combat drug resistance is to provide rapid, reliable and sensitive diagnostic methods in health care centres. This study focuses on development of an effective pipeline to identify drug resistance mutations in whole genome data of Mycobacterium tuberculosis utilizing the Next Generation Sequencing approach and classification of drug resistance strains based on genetic markers obtained from TGS-TB, tbvar and TBDReamDB. 74 isolates are characterized into 20 DR-TB, 16 MDR-TB, 16 XDR-TB and 6 nonresistant strains based on known drug resistance genetic markers. Results provide mutation pattern for each of the classified strains and profiling of drug resistance to the group of anti-TB drugs. The presence of specific mutation causing resistance to a drug will help set the dosage levels which play an important role in the treatment. Findings on amino acid changes and its respective codon positions in candidate genes will provide insights in drug sensitivity and a way for discovery of potent drugs. The implementation of these approaches in clinical setting provides rapid and sensitive diagnostics to combat the emerging drug resistance.

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