Telithromycin inhibition of protein synthesis and 50S ribosomal subunit formation in Streptococcus pneumoniae cells.
The new ketolide antibiotic telithromycin (HMR3647) has been examined for inhibitory effects in cells of Streptococcus pneumoniae. The antibiotic caused a proportional decline in cell growth rate and viability with an IC(50) of 15 ng/ml. At a concentration of 7.5 ng/ml, protein synthesis in these cells was reduced by 50%. As seen in other organisms, this compound was also a very effective inhibitor of the formation of the 50S ribosomal subunit in growing cells. Pulse and chase labeling assays defined the reduced rate of 50S synthesis in antibiotic treated cells. At 7.5 ng/ml the rate was reduced to 50% of the control synthesis rate. An IC(50) of 15 ng/ml was found for the effect on this process. 30S ribosomal subunit formation was unaffected by the antibiotic. Inhibition of translation and 50S particle formation are equivalent targets for this antibiotic. The effects of telithromycin in S. pneumoniae are compared with those found in Staphylococcus aureus cells.
Champney
W Scott
WS
Department of Biochemistry and Molecular Biology, J.H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. champney@etsu.edu
Pelt
Jennifer
J
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D048628:Ketolides; D018942:Macrolides; D011500:Protein Synthesis Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism
D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D011500:Protein Synthesis Inhibitors; C106791:telithromycin; D014529:Uridine