The ketolide antibiotic ABT-773 is a specific inhibitor of translation and 50S ribosomal subunit formation in Streptococcus pneumoniae cells.
ABT-773 is a new 3-keto macrolide antibiotic that has been shown to be very effective against infections by Gram-positive microorganisms. This work examines its inhibitory effects in cells of Streptococcus pneumoniae. ABT-773 caused a proportional decline in cell growth rates and viability with an IC(50) of 5 ng/ml. Protein synthesis in these cells was reduced by 50% at an antibiotic concentration of 2.5 ng/ml. This compound was also found to be a very effective inhibitor of the formation of the 50S ribosomal subunit in growing cells. Pulse and chase labeling assays revealed a reduced rate of 50S synthesis in antibiotic-treated cells. At 2 ng/ml, the rate was reduced to 33% of the control synthesis rate. An IC(50) of 5 ng/ml was found for the effect on this process, indicating an equal effect of the drug on translation and assembly. Synthesis of the 30S ribosomal subunit was unaffected by this antibiotic. The effects of ABT-773 in S. pneumoniae are compared with those of the related ketolide antibiotic telithromycin in S. pneumoniae and in Staphylococcus aureus.
Department of Biochemistry and Molecular Biology, J.H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA. champney@etsu.edu
W Scott
WS
Champney
Jennifer
J
Pelt
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D048628:Ketolides; D018942:Macrolides; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D014176:Protein Biosynthesis / Q000187:drug effects; D012270:Ribosomes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D004917:Erythromycin; C405499:cethromycin; C106791:telithromycin