Protein synthesis in Mycobacterium tuberculosis as a potential target for therapeutic interventions

Abstract

Mycobacterium tuberculosis (Mtb) causes one of humankind's deadliest diseases, tuberculosis. Mtb protein synthesis machinery possesses several unique species-specific features, including its ribosome that carries two mycobacterial specific ribosomal proteins, bL37 and bS22, and ribosomal RNA segments. Since the protein synthesis is a vital cellular process that occurs on the ribosome, a detailed knowledge of the structure and function of mycobacterial ribosomes is essential to understand the cell's proteome by translation regulation. Like in many bacterial species such as Bacillus subtilis and Streptomyces coelicolor, two distinct populations of ribosomes have been identified in Mtb. Under low-zinc conditions, Mtb ribosomal proteins S14, S18, L28, and L33 are replaced with their non-zinc binding paralogues. Depending upon the nature of physiological stress, species-specific modulation of translation by stress factors and toxins that interact with the ribosome have been reported. In addition, about one-fourth of messenger RNAs in mycobacteria have been reported to be leaderless, i.e., without 5′ UTR regions. However, the mechanism by which they are recruited to the Mtb ribosome is not understood. In this review, we highlight the mycobacteria-specific features of the translation apparatus and propose exploiting these features to improve the efficacy and specificity of existing antibiotics used to treat tuberculosis.