Practice question

Protein synthesis machinery is highly conserved across domains yet bacterial 70S ribosomes differ structurally and compositionally from eukaryotic 80S ribosomes sufficiently to allow selective toxicity. Tetracycline is considered broad-spectrum because it penetrates both Gram-positive and Gram-negative envelopes via OmpF and OmpC porins and active transport, chelating Mg2+ to cross membranes as metal complex. It binds reversibly to a high-affinity pocket on the 30S small subunit, specifically helix 34 of 16S rRNA near the A-site where codon-anticodon interaction occurs. Binding sterically blocks accommodation of aminoacyl-tRNA into the A-site, preventing addition of new amino acid residues to the growing polypeptide chain without affecting peptidyl transferase center directly. Unlike more selective Gram-positive agents such as penicillin G or vancomycin that target peptidoglycan cross-linking, or bacitracin that blocks recycling of C55 lipid carrier, tetracycline inhibits essentially all bacterial translation including Gram-positives, Gram-negatives, atypicals and protozoa. Resistance arises via efflux pumps encoded by tetA and tetB and ribosomal protection proteins tetM and tetO that dislodge drug, widespread due to plasmid spread.