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Antimicrobial Agents and Chemotherapy, June 2006, p. 2042-2049, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.01411-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inhibition of Mammalian Mitochondrial Protein Synthesis by Oxazolidinones

E. E. McKee,1* M. Ferguson,1 A. T. Bentley,1 and T. A. Marks2,{dagger}

Indiana University School of Medicine—South Bend, South Bend, Indiana 46617,1 Pharmacia Corporation, Kalamazoo, Michigan 490012

Received 1 November 2005/ Returned for modification 1 December 2005/ Accepted 5 April 2006

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.

* Corresponding author. Mailing address: Indiana University School of Medicine—South Bend, 1234 Notre Dame Avenue, South Bend, IN 46617. Phone: (574) 631-7193. Fax: (574) 631-7821. E-mail: McKee.6{at}nd.edu.

{dagger} Present address: Safety Assessment US, AstraZeneca LP, Chesapeake 2C-522, P.O. Box 15437, Wilmington, DE 19850-5437.

Antimicrobial Agents and Chemotherapy, June 2006, p. 2042-2049, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.01411-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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