Therapeutic Targeting of Protein Tyrosine Phosphatases from Mycobacterium tuberculosis

Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the World Health Organization, an estimated 10 million people developed TB in 2018. The occurrence of drug-resistant TB demands therapeutic agents with novel mechanisms of action. Antivirulence is an alternative strategy that targets bacterial virulence factors instead of central growth pathways to treat disease. Mycobacterium protein tyrosine phosphatases, mPTPA and mPTPB, are secreted by Mtb into the cytoplasm of macrophages and are required for survival and growth of infection within the host. Here we present recent advances in understanding the roles of mPTPA and mPTPB in the pathogenesis of TB. We also focus on potent, selective, and well-characterized small molecule inhibitors reported in the last decade for mPTPA and mPTPB.

Automated summary

Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis, and the treatment of drug-resistant TB requires therapeutic agents with novel mechanisms. Antivirulence, focusing on bacterial virulence factors, is an alternative strategy for treating diseases. Recent advances in understanding the roles of mPTPA and mPTPB in the pathogenesis of TB have been made, along with the discovery of potent, selective, and well-characterized small molecule inhibitors for these proteins in the past decade.