Mycobacterium tuberculosis targets related to trans-translation and coenzyme A synthesis

This target entry refers to a group of essential proteins in Mycobacterium tuberculosis that are inhibited by the front-line antibiotic pyrazinamide (PZA). The primary components include Ribosomal protein S1 (RpsA), which is vital for the trans-translation pathway used to rescue stalled ribosomes, and Aspartate decarboxylase (PanD), a key enzyme in the synthesis of Coenzyme A (CoA). Pyrazinoic acid, the active metabolite of PZA, binds to RpsA to disrupt protein translation under stress conditions and targets PanD to deplete the bacterium's CoA pool. These mechanisms are particularly effective against non-replicating, persistent mycobacteria that reside in acidic environments like the phagolysosome. Historically, the exact molecular targets of PZA were described as unclear because the drug requires activation by the bacterial enzyme pyrazinamidase (PncA) and affects multiple metabolic pathways simultaneously. Understanding these targets is critical for addressing drug resistance, as mutations in pncA, rpsA, or panD can lead to clinical PZA resistance. Consequently, these proteins represent a complex but vital focal point for anti-tubercular drug development and efficacy monitoring.

Other names

Ribosomal protein S1RpsAAspartate decarboxylasePanDPyrazinamide targetsRv1630Rv3601c

Inhibition of the trans-translation process by binding to Ribosomal protein S1 (RpsA) and inhibition of Coenzyme A biosynthesis by targeting Aspartate decarboxylase (PanD).