[Source: Antimicrobial Agents Chemotherapy, full page: (LINK). Abstract, edited.]
Solithromycin Inhibition of Protein Synthesis and Ribosome Biogenesis in Staphylococus aureus, Streptococcus pneumoniae, and Haemophilus influenzae
Ward Rodgers, Ashley D. Frazier and W. Scott Champney
Author Affiliations: Department of Biomedical Sciences, J.H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
The continuing increase in antibiotic resistant microorganisms is driving the search for new antibiotic targets and improved antimicrobial agents. Ketolides are next generation semi-synthetic derivatives of macrolide antibiotics, which are effective against certain resistant organisms. Solithromycin (CEM-101) is a novel fluoroketolide with improved antimicrobial effectiveness. This compound binds to the large 50S subunit of the ribosome and inhibits protein biosynthesis. Like other ketolides, it should impair bacterial ribosomal subunit formation. This mechanism of action was examined in strains of Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. The mean IC50 values for solithromycin inhibition of cell viability, protein synthesis and growth rate were 7.5, 40 and 125ng/mL for Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae, respectively. The net formation of the 50S subunit was reduced in all three organisms with IC50 values similar to those above. The rates of 50S subunit formation measured by a pulse and chase labeling procedure were reduced by 75% in cells growing at the IC50 concentration of solithromycin. Turnover of 23S rRNA was stimulated by solithromycin as well. Solithromycin was found to be a particularly effective antimicrobial agent with IC50 values comparable to telithromycin and significantly better than azithromycin and clarithromycin in these three microorganisms.
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