## 6 Acquired Drug-Resistance of Mtb
Useful information was provided on what it is currently in TB diagnostics, including tests already recommended by the WHO, and on which tests are expected to be available soon. As to the decentralized tests, the Xpert MTB/RIF assay (sensitivity and specificity for RIF resistance of 96% and 98%, respectively) was recommended by the WHO in 2010, and entered in the market in the same year. The sensitivity of this assay increased with the 2017 rollout of the Xpert MTB/RIF Ultra cartridge. In 2020, there is expected the WHO evaluation and market entry of Xpert XDR, which will detect resistance to INH, \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Group** & **Drug** & **Target Gene/s** & **Gene Product (Function Affected)** & **References** \\ \hline  & & _rpsA_ & 30S ribosomal protein S1 (m-RNA & [23, 111] \\  & & & trans-translation) & \\ \hline  & & _panD_ & \begin{tabular}{c} Aspartate decarboxylate \\ (pathionate synthesis) \\ \end{tabular} & [111, 112] \\ \hline  & & _clpc1_ & \begin{tabular}{c} ATP-dependent ATP-ase (protein \\ degradation) \\ \end{tabular} & [23, 113] \\ \hline  & IPM-CLN & _rv2518c_ & \begin{tabular}{c} LdtB, nonclassical, l,-transpeptidase \\ (peptidoglycan synthesis) \\ \end{tabular} & [19, 54, 114, 115] \\ \hline  & & _rv3682_ & \begin{tabular}{c} PonA2, penicillin-binding protein \\ (peptidoglycan synthesis) \\ \end{tabular} & [19, 114] \\ \hline  & & _Rv2068c_ & blaC (\(\beta\)-lactamase) & [116] \\ \hline  & AM & _rrs_ & \begin{tabular}{c} 16S ribosomal RNA (protein \\ synthesis) \\ \end{tabular} & [98, 117] \\ \hline  & SM & _rpsl_ & ribosomal protein S12 (protein \\  & & & synthesis) \\ \hline  & & _rrs_ & \begin{tabular}{c} 16S ribosomal RNA (protein \\ synthesis) \\ \end{tabular} & [98, 117] \\ \hline  & & _gitB_ & \begin{tabular}{c} (putative 16S rRNA \\ methyltransferase) \\ \end{tabular} & [119, 120] \\ \hline  & ETO or PTO & _rv0565c_ & \begin{tabular}{c} Monoxygenase (activation of \\ pro-drugs ETO and PTO) \\ \end{tabular} & [121] \\ \hline  & _ethA_ & \begin{tabular}{c} Monoxygenase (activation of ETO \\ and PTO) \\ \end{tabular} & [19, 122] \\ \hline  & _mymA_ & \begin{tabular}{c} Monoxygenase (activation of ETO \\ and PTO) \\ \end{tabular} & [121, 123] \\ \hline  & _katG_ & \
\begin{tabular}{c} Catalase-peroxidase (activation of \\ ETO, PTO, INH) \\ \end{tabular} & [122] \\ \hline  & _inhA_ &
\begin{tabular}{c} Enoyl-ACP reductase (mycolic acid \\ synthesis) \\ \end{tabular} & [98, 122] \\ \hline  & PAS & _thyA_ & Thymidylate synthase & [23, 124] \\ \hline  & _folC_ & Dihydropholate synthase & [23, 125] \\ \hline  & _dfrA_ & Dihydropholate reductase & [23, 125] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: _Cont._MFX, OFL, AK and KM [129]. In 2013, another company (Molbio Diagnostics, Goa, India) released its systems Truenat MTB and Truenat MTB-RIF Dx onto the Indian market [129]. In January 2020, a rapid WHO Communication reported that the Truenat systems MTB, MTB Plus and MTB RIF Dx assays showed comparable accuracy with Xpert MTB/RIF and Xpert Ultra for Mtb detection (Truenat MTB and Truenat MTB Plus), and for sequential RIF resistance detection (Truenat MTB RIF Dx) [130]. Furthermore, the data for Truenat MTB RIF Dx showed similar accuracy to the WHO approved commercial line probe assays indicated by the TAG for centralized DST [GenoType MTBDR_plus_ Version 2.0 (Hain Lifescience, Nehren, Germany) and Nipro NTM+MDRTB detection kit2 (Nipro, Osaka, Japan)] [129,130]. Other systems marketed in 2015-2019 and on the pathway to the WHO evaluation for the centralized determination of molecular resistance to INH and RIF are: Cobas MTB-RIF/INH (Roche, Basel, Switzerland), BD MAX MDR-TB (Becton Dickinson, Sparks, MA, USA), real-time MTB-RIF/INH Resistance assay (Abbott, Abbott Park, IL, USA) and FluoroType MTBDR version 2.0 (RIF, INH) (Hain Lifescience) [129,131,132,133]. Finally, the WGS technology is capable of identifying the complete drug-resistance profile of an Mtb strain, ideally enabling clinicians to obtain the best anti-TB treatment [98,128,130,134].