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Novel Antibiotic Discovered in Worms Antibiotics that inhibit bacterial protein synthesis bind to bacterial ribosomes in ways that are distinct from their binding to eukaryotic ribosomes, which explains their specificity. The antibiotic chloramphenicol specifically targets the bacterial 50S ribosomal subunit, whereas aminoglycosides such as spectinomycin specifically target the bacterial 30S ribosomal subunit. Bacterial resistance to aminoglycosides is a major health problem, and this has led researchers to search for next- generation antibiotics. One class of these new antibiotics is called odilorhabdins, which are produced by symbiotic bacteria that live inside parasitic nematodes. Odilorhabdins are pseudopeptides that bind to a unique site in the 30S bacterial ribosome and, like aminoglycosides, cause errors in tRNA binding and misreading of the mRNA transcript. Paromomycin

eukaryotes. Puromycin is structurally similar to the terminal aminoacyl-adenosine of tRNA and binds to the A site of ribosomes (Figure 22.24). Puromycin acts as an acceptor for the growing polypeptide chain and causes premature termination of translation. Puromycin was used to confirm that the rRNA functions as a ribozyme and participated directly in the formation of the peptide bond between the growing polypeptide chain and the amino acid charged to the tRNA in the A site.

As shown in Figure 22.25, chloramphenicol and erythromycin both bind to the 50S subunit and inhibit elongation by affecting peptide bond formation or ribosome translocation, respectively. In contrast, streptomycin and tetracyclines impair ribosomal function leading to defective protein synthesis. Streptomycin binds to the 30S ribosome and disrupts base pairing between the mRNA codon and tRNA anticodon. Tetracyclines prevent the interaction between charged tRNA and the ribosomal A site, thus inhibiting elongation. These particular antibiotics inhibit ribosomal function in bacteria but have little or no effect on general protein synthesis in eukaryotes because of structural differences between the prokaryotic and eukaryotic ribosomes.

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