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Antimicrobial Agents and Chemotherapy, June 2000, p. 1413-1417, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Evernimicin (SCH27899) Inhibits both Translation and 50S Ribosomal Subunit Formation in Staphylococcus aureus Cells

W. Scott Champney* and Craig L. Tober

Department of Biochemistry and Molecular Biology, J. H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614

Received 29 June 1999/Returned for modification 24 December 1999/Accepted 17 February 2000

The effects of the everninomicin antibiotic evernimicin (SCH27899) on growing Staphylococcus aureus cells were investigated. Cellular growth rates and viable cell numbers decreased with increasing antibiotic concentrations. The rate of protein synthesis, measured as 35S-amino acid incorporation, declined in parallel with the growth rate. Significantly, the formation of the 50S ribosomal subunit was inhibited in a dose-dependent fashion as well. 30S ribosomal subunit synthesis was not affected over the same concentration range. Evernimicin did not stimulate the breakdown of mature ribosomal subunits. Pulse-chase labeling experiments revealed a reduced rate of 50S subunit formation in drug-treated cells. Two erythromycin-resistant strains of S. aureus that carried the ermC gene were as sensitive as wild-type cells to antibiotic inhibition. In addition, two methicillin-resistant S. aureus organisms, one sensitive to erythromycin and one resistant to the macrolide, showed similar sensitivities to evernimicin. These results suggest a use for this novel antimicrobial agent against antibiotic-resistant bacterial infections.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, J. H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614. Phone: (423) 439-4651. Fax: (423) 439-8235. E-mail: champney{at}etsu.edu.

Antimicrobial Agents and Chemotherapy, June 2000, p. 1413-1417, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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