# Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs
## 5 Conclusions  
In 1882, when [PERSON] discovered the causative agent of TB, there was no valid treatment for the disease. In the past 70 years, with the introduction of multidrug chemotherapy, the cure rate for drug-susceptible _M. tuberculosis_ infection has reached up to 95%. The treatment is effective but very long, with drugs that may not be well tolerated. New chemotherapy regimens are needed with drugs that are less toxic and more efficacious, so that a shorter treatment can be achieved. The pursuit of mycobacterial cell wall inhibitors has offered several hits with novel modes of action and remarkable potency that have reached clinical trials. Those pioneering compounds can lead the way to more valuable therapeutics. Numerous new compounds are being studied that either derive from the known hits or target other biosynthetic pathways of the cell wall [261; 262]. In the past 20 years, _M. tuberculosis_ has been unraveling many of its secrets: its niches in the host, its metabolism and its way of fighting drugs. New tools were developed to study _M. tuberculosis_ and to search for new TB drugs more efficiently combining target and whole-cell screenings. We should be closer to a new TB regimen for a shorter treatment of drug-susceptible TB and a more successful treatment of MDR and XDR TB. The collaboration between academic and pharmaceutical laboratories and the involvement of funding foundations have opened the doors to the clinical testing of new drugs and new regimens [263].  
In [PERSON]'s book \"The Conquest of Tuberculosis\" [264], a quote from [PERSON]'s speech at the 1961 Sixteenth International Conference on Tuberculosis, as reported by the chairman, stated: \"We are not concerned with eradication in the absolutely literal sense of the word because this is something that many of us believe to be biologically impossible. What we are talking about, however, is tuberculosis 'eradication' in the sense of reducing the problem to the point where the disease is a scientific curiosity. This is a biologic possibility\". With better diagnostic tools, a more efficient vaccine and sterilizing therapeutics, this might become a biologic reality.  
A summary of the cell wall inhibitors discussed herein is presented in Table 1 with their chemical structures and targets.  
\begin{table}
\begin{tabular}{|c|c|c|c|c|} \hline
**Name** & **Structure** &
\begin{tabular}{c} **Cell Wall Component** \\ **Inhibited** \\ \end{tabular} & **Prodrug/Activator** & **Target** \\ \hline Isoniazid & & Mycolic acids & + & InhA \\  & & & KatG & \\ \hline Ethionamide & & Mycolic acids & EthA, MymA, Rv0565c & InhA \\  & ETH & PTH & & \\ \hline Thiaacetazone & & Mycolic acids & + & HadAB \\  & & & EthA & \\ \hline Pretonamid & & & & \\ \hline \end{tabular}
\end{table}
Table 1: TB drugs targeting the mycobacterial cell wall.  
\begin{table}
\begin{tabular}{|c|c|c|c|c|} \hline
**Name** & **Structure** & **Cell Wall Component** & **Prodrug/Activator** & **Target** \\ \hline Delamamid & & Methoxy- and keto-mycolic acids & + Ddn &? \\ \hline SQ109 & & Mycolic acid transport & - & Mmpl3 \\ \hline CPZEN45 & & Arabinogalactan & - & WeCA \\ \hline Ethambutol & & Arabinogalactan LAM & - & EmbCAB \\ \hline BTZ043 & & Arabinogalactan LAM & + & DprE1 \\ \hline PBTZ169 & & Arabinogalactan LAM & + & DprE1 \\ \hline OPC167832 & & Arabinogalactan LAM & + & DprE1 \\ \hline TBA/371 & & Arabinogalactan LAM & - & DprE1 \\ \hline Cycloserine & & Peptidoglycan & - & DdIA \\ \hline \end{tabular}
\end{table}
Table 1: _Cont._  
**Funding:** CV acknowledges support through grant AI21670 from the US National Institutes of Health.  
**Acknowledgments:** I thank [PERSON], [PERSON] and [PERSON] for their critical reading, comments and feedback on this manuscript.  
**Conflicts of Interest:** The author declares no conflict of interest.