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Mycobacterium tuberculosis protein synthesis machinery (Mtb protein synthesis machinery)

Target
Mtb protein synthesis machinery
Molecular classification
Ribonucleoprotein complex, Enzyme, Protein-RNA complex
01

Overview

The Mycobacterium tuberculosis protein synthesis machinery is a complex ribonucleoprotein system responsible for translating genetic information into functional proteins, a process essential for the survival, growth, and pathogenesis of the bacterium (Wilson, 2014, Nature Reviews Microbiology). It primarily consists of the 70S ribosome, which is composed of the 30S and 50S subunits, along with various initiation, elongation, and termination factors (Shasmal & Nayak, 2021, Journal of Molecular Biology). This machinery is a cornerstone of anti-tuberculosis therapy, as several classes of antibiotics specifically target different components of the ribosome to disrupt bacterial translation (Krause et al., 2016, Cold Spring Harbor Perspectives in Medicine). For instance, aminoglycosides like streptomycin bind to the 16S rRNA of the 30S subunit to cause misreading of mRNA, while oxazolidinones like linezolid bind to the 23S rRNA of the 50S subunit to inhibit the formation of the initiation complex (Diekema & Jones, 2001, Lancet). Because the bacterial ribosome differs significantly in structure from the eukaryotic ribosome, it allows for selective toxicity against M. tuberculosis (Poehlsgaard & Douthwaite, 2005, Nature Reviews Microbiology). However, the emergence of drug-resistant strains through mutations in ribosomal RNA (e.g., rrs or rrl genes) or proteins (e.g., rpsL) remains a significant challenge in global health (Georghiou et al., 2012, PLOS ONE). Effective targeting of this machinery is crucial for treating both drug-susceptible and multi-drug-resistant tuberculosis infections.

Other names
Mycobacterium tuberculosis ribosomeMtb translational machineryMtb protein synthesis apparatusMycobacterium tuberculosis 70S ribosome
02

Mechanism of action

Inhibition of bacterial protein synthesis by binding to the 30S or 50S ribosomal subunits, thereby interfering with mRNA decoding, tRNA binding, or peptide bond formation (Wilson, 2014, Nature Reviews Microbiology).

03

Biological functions

Protein synthesisTranslationPeptidyl transferTranslocationmRNA decoding
04

Disease associations

TuberculosisInfection
05

Safety considerations

Ototoxicity (aminoglycosides)Nephrotoxicity (aminoglycosides)Myelosuppression (oxazolidinones)Peripheral neuropathy (oxazolidinones)Optic neuropathy (oxazolidinones)Development of multi-drug resistance (MDR-TB)
06

Interacting drugs

Streptomycin

9 more in the full profile.

07

Biomarkers

rrs gene mutations (aminoglycoside resistance)rpsL gene mutations (streptomycin resistance)rrl gene mutations (oxazolidinone/macrolide resistance)Sputum culture conversionTime to positivity (TTP) in liquid culture

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