Newer regimen for drug resistant-tuberculosis: A ray of hope or threatening shadows

Various gene mutations are identified as culprits in Bdq-resistance, including atpE, which encodes ATP synthase (the BDQ target), and Rv0678, Rv0677c, and pepQ.Additionally, mutations in the intergenic region between Rv0678 (efflux pump MmpL5) and Rv0677c (efflux pump MmpS5) suppress ATP synthase inactivity.These mutations are often induced by factors like improper use, inadequate dosing, and inconsistent adherence to treatment protocols. [7]rrent studies highlight the effectiveness of combining genomic tools with rapid phenotypic diagnostics to detect Bdq resistance in MTB isolates. [9]Genotypic methods include Whole Genome Sequencing (WGS) and targeted gene sequencing for specific mutations in atpE, pepQ, and Rv0678.Other genotypic methods are PCR-based techniques, Line Probe Assays (LPAs), CRISPR-Cas9-based methods, microarray technology, and Next-Generation Sequencing (NGS).Phenotypic methods for detecting Bdq resistance include the Agar Proportion Method (APM), Minimum Inhibitory Concentration (MIC) testing, the Bactec MGIT 960 system with Bdq, the Resazurin Microtiter Assay (REMA), luciferase reporter assays, the Alamar Blue assay, and time-kill assays. [9]Phenotypic methods, such as the Agar Proportion Method, while considered the gold standard, have a lower limit of detection for minority-resistant populations compared to molecular tests like Target and WGS. [8]Even PCR based diagnostic methods can only detect a limited number of genetic mutations already known to confer drug resistance.In contrast, whole genome sequencing (WGS) has the ability to interrogate the entire genome sequence of a bacterium and enables the detection of multiple novel mutations that may be associated with drug resistance. [10]epending on the sequencing platform and culture method used to grow MTB, results can be achieved in as little as 7 days and have the capacity to identify a broad range of genetic polymorphisms, which can help to develop new treatment strategies and improve the case management for DR-TB.Thus, many of the limitations of PCR-based diagnostic and drug resistance detection methods can be overcome by WGS to provide genome-wide insight into emerging clinically relevant mutations in the MTB.