Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones.
The effects of a variety of oxazolidinones, with different antibacterial potencies, including linezolid, on mitochondrial protein synthesis were determined in intact mitochondria isolated from rat heart and liver and rabbit heart and bone marrow. The results demonstrate that a general feature of the oxazolidinone class of antibiotics is the inhibition of mammalian mitochondrial protein synthesis. Inhibition was similar in mitochondria from all tissues studied. Further, oxazolidinones that were very potent as antibiotics were uniformly potent in inhibiting mitochondrial protein synthesis. These results were compared to the inhibitory profiles of other antibiotics that function by inhibiting bacterial protein synthesis. Of these, chloramphenicol and tetracycline were significant inhibitors of mammalian mitochondrial protein synthesis while the macrolides, lincosamides, and aminoglycosides were not. Development of future antibiotics from the oxazolidinone class will have to evaluate potential mitochondrial toxicity.
McKee
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Indiana University School of Medicine--South Bend, IN 46617, USA. McKee.6@nd.edu
Ferguson
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Bentley
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Marks
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002701:Chloramphenicol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D015394:Molecular Structure; D010080:Oxazoles / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D013752:Tetracycline / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D010080:Oxazoles; D011500:Protein Synthesis Inhibitors; D002701:Chloramphenicol; D013752:Tetracycline