Bacterial ribosome

Category: catabolism

Overview

Bacterial 70S ribosome (30S + 50S) is the major antibiotic target — selective toxicity arises from the eukaryotic 80S ribosome's structural differences (40S + 60S). 30S inhibitors: tetracyclines block aminoacyl-tRNA A-site loading (bacteriostatic); aminoglycosides bind 16S rRNA → mistranslation + membrane permeabilization (bactericidal). 50S inhibitors: macrolides + ketolides bind 23S rRNA peptidyl-transferase loop → premature peptide chain release (bacteriostatic, partly bactericidal at high conc); lincosamides (clindamycin) bind near macrolide site → cross-resistance via MLSb mechanism; oxazolidinones (linezolid) prevent 70S initiation complex assembly; chloramphenicol blocks peptidyltransferase. Aminoglycoside-induced ototoxicity + nephrotoxicity reflects accumulation in cochlear hair cells + renal tubular cells.

Organ Systems

• immune-hematologic

Pathway Steps

1. bacterial-ribosome → peptide-elongation — via 70S assembly + aminoacyl-tRNA loading at A-site → peptide bond formation → translocation. The bacterial 70S ribosome (30S + 50S) differs enough from the eukaryotic 80S to be a major selective antibiotic target. Drug classes hit distinct steps: aminoglycosides and tetracyclines act on the 30S (decoding), while macrolides, chloramphenicol, and oxazolidinones act on the 50S (peptide-bond formation/elongation).

Known Modulators

• erythromycin (inhibitor) — 50S (23S rRNA, peptidyl-transferase). first macrolide; strong CYP3A4 inhibitor (multi-DDI perpetrator); GI motility side effect via motilin agonism (used off-label for gastroparesis)
• clarithromycin (inhibitor) — 50S (23S rRNA). macrolide; strong CYP3A4 inhibitor; H. pylori triple-therapy component; QT prolongation
• azithromycin (inhibitor) — 50S (23S rRNA). azalide macrolide; weak CYP3A4 inhibitor (vs erythromycin/clarithromycin); long tissue half-life → short-course dosing; QT prolongation
• telithromycin (inhibitor) — 50S (23S rRNA). ketolide; designed for macrolide-resistant pneumococcus; hepatotoxicity + myasthenia exacerbation withdrew it 2007
• doxycycline (inhibitor) — 30S (16S rRNA, A-site). tetracycline; broad-spectrum + intracellular pathogens (Rickettsia, Chlamydia); avoid divalent cations (Ca/Mg/Fe — separate by 2h)
• minocycline (inhibitor) — 30S (16S rRNA, A-site). tetracycline; CNS-penetrant (acne + neuroinflammatory off-label); divalent-cation chelation same as doxycycline
• gentamicin (inhibitor) — 30S (16S rRNA — mistranslation). aminoglycoside; gram-negative bactericidal; nephrotoxicity + ototoxicity require trough monitoring
• tobramycin (inhibitor) — 30S (16S rRNA). aminoglycoside; pseudomonal activity > gentamicin; inhaled form for CF airway
• linezolid (inhibitor) — 50S (23S rRNA, initiation complex). oxazolidinone; MRSA + VRE active; weak MAOI → serotonin-syndrome risk with SSRIs; mitochondrial toxicity at chronic use (>28 days)
• clindamycin (inhibitor) — 50S (23S rRNA, near macrolide site). lincosamide; anaerobe + gram-positive; canonical C. difficile precipitant (highest-risk antibiotic for CDI)

References

• PMID 29570352