Chloramphenicol

Chloramphenicol is an antiribosomal antibiotic that was isolated from Streptomyces venezuelae. It was initially used as a broad spectrum antibiotic before being withdrawn from clinical use in the West, due to concerns that it may increase the risk of aplastic anemia. Chloramphenicol remains in use in other parts of the world. Chloramphenicol is a structural analog of aminoacyl-tRNA, which initially hinted at its mechanism of action. Its mechanism of action involves inhibition of protein synthesis by binding to the bacterial ribosome and inhibiting the formation of the peptide bond. Chloramphenicol accomplishes this by inhibiting ribosomal peptidyl transferase activity. This can be demonstrated using a peptidyl transferase reaction mix containing ribosomal subunits and \({ }^{35}\) S-CAACCA-formyl-methionine. Puromycin, another protein synthesis inhibitor, can be used to confirm the chloramphenicol-induced inhibition of peptide bond formation. Chloramphenicol resistance is caused by mutations to the 23S rRNA, chloramphenicol acetyltransferases, 3-O-phosphorylation of the chloramphenicol molecule, and by multidrug efflux pumps.