Ribosomal protein S1 (RpsA) (RpsA)

Ribosomal protein S1 (RpsA) is a vital component of the 30S ribosomal subunit in Mycobacterium tuberculosis, playing a critical role in both canonical translation and the trans-translation process. Trans-translation is a quality-control mechanism that rescues stalled ribosomes and tags incomplete polypeptides for degradation, which is particularly important for the survival of non-replicating "persister" bacilli during latent infection. Pyrazinamide (PZA), a cornerstone of first-line tuberculosis therapy, acts as a prodrug that is converted by the bacterial enzyme pyrazinamidase into its active form, pyrazinoic acid (POA). POA binds to RpsA, thereby inhibiting trans-translation and leading to the accumulation of toxic protein products and the depletion of functional ribosomes. While RpsA is a major ribosome-associated target, PZA is also known to affect other targets such as aspartate 1-decarboxylase (PanD) and disrupt membrane energetics, contributing to its unique ability to kill dormant mycobacteria in acidic environments.

Other names

30S ribosomal protein S1RpsAPyrazinamide targetAspartate 1-decarboxylase (PanD)Fatty acid synthase I (FAS I)

Pyrazinamide is a prodrug converted to pyrazinoic acid (POA) by bacterial pyrazinamidase. POA binds to Ribosomal protein S1 (RpsA), inhibiting trans-translation, a process essential for rescuing stalled ribosomes and maintaining protein synthesis in non-replicating persisters. It also inhibits Aspartate 1-decarboxylase (PanD), triggering its degradation and disrupting coenzyme A biosynthesis.