Resumen de Chapter Fourteen - Advancement of Cell Wall Inhibitors in Mycobacterium tuberculosis
Pravin S. Shirude, Monalisa Chatterji, Shridhar Narayanan, Pravin S. Iyer
Abstract Despite decades of scientific progress, tuberculosis (TB) still remains a major global health problem. The first-line and second-line anti-TB drugs include compounds that inhibit some part of Mycobacterium tuberculosis (Mtb) cell wall synthesis or metabolism. The recent understanding of “cell wall core” activity in the different stages of infection in vivo has highlighted the importance of cell wall inhibitors targeting both replicating and nonreplicating Mtb. Therefore, most of the newly discovered compounds emphasize the cell wall as the target of choice for Mtb. Drug-to-target screening approaches have identified novel targets impacting major cell wall components (e.g., DprE1, MmpL3, and others) in addition to better known targets (InhA, peptidoglycan synthesis). Novel cell wall inhibitors provide a potential new therapy to address drug-resistant TB in patients who are resistant to existing first- and second-line drugs. This review broadly describes recent advances in targeting the cell wall of Mtb, with specific focus on InhA, DprE1, MmpL3, and peptidoglycan biosynthesis.
