The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause extensive translational inaccuracy in vivo

The oxazolidinone family is a new class of synthetic antibiotics that bind to the bacterial 50 S ribosomal subunit. Two members of the family, linezolid and XA043, were examined for their effects on translational fidelity using a lac Z reporter gene in vivo. Both promoted highly significant frameshifting and nonsense suppression. Chloramphenicol, a peptidyl transferase inhibitor, affected translational fidelity in a similar fashion. Neither the oxazolidinones nor chloramphenicol stimulated misincorporation of amino acid residues at position 461 in the lac Z gene. In contrast, the aminoglycosides gentamicin and paromomycin, which interact with the decoding region of the 30 S subunit, caused significant misincorporation but only modest increases in frameshifting or stop codon readthrough of the lac Z gene. We conclude that effects on translational fidelity may play a significant role in the mechanism of action of the oxazolidinones. (C) 2002 Elsevier Science Ltd. All rights reserved.