Novel Treatments against Mycobacterium tuberculosis Based on Drug Repurposing

Abstract

Tuberculosis is the leading cause of death, worldwide, due to a bacterial pathogen. This respiratory disease is caused by the intracellular pathogen Mycobacterium tuberculosis and produces 1.5 million deaths every year. The incidence of tuberculosis has decreased during the last decade, but the emergence of MultiDrug-Resistant (MDR-TB) and Extensively Drug-Resistant (XDR-TB) strains of M. tuberculosis is generating a new health alarm. Therefore, the development of novel therapies based on repurposed drugs against MDR-TB and XDR-TB have recently gathered significant interest. Recent evidence, focused on the role of host molecular factors on M. tuberculosis intracellular survival, allowed the identification of new host-directed therapies. Interestingly, the mechanism of action of many of these therapies is linked to the activation of autophagy (e.g., nitazoxanide or imatinib) and other well-known molecular pathways such as apoptosis (e.g., cisplatin and calycopterin). Here, we review the latest developments on the identification of novel antimicrobials against tuberculosis (including avermectins, eltrombopag, or fluvastatin), new host-targeting therapies (e.g., corticoids, fosfamatinib or carfilzomib) and the host molecular factors required for a mycobacterial infection that could be promising targets for future drug development.

Keywords: Mycobacterium tuberculosis; drug repurposing; host-directed therapies; multidrug-resistant strains.

Figure 1

(A) Activity of some repurposed antimicrobials against M. tuberculosis. (B) Mechanism of action of some host-directed therapies to inhibit intracellular M. tuberculosis proliferation.