**5. Conclusions**

In 1882, when Robert Koch 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 Selman Waksman's book "The Conquest of Tuberculosis" [264], a quote from Georges Canetti'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.


**Table 1.** TB drugs targeting the mycobacterial cell wall.




**Table 1.** *Cont*.

**Funding:** CV acknowledges support through grant AI21670 from the US National Institutes of Health.

**Acknowledgments:** I thank Lawrence Leung, Claire Mulholland and Saranathan Rajagopalan for their critical reading, comments and feedback on this manuscript.

**Conflicts of Interest:** The author declares no conflict of interest.
