Solithromycin Inhibition of Protein Synthesis and Ribosome Biogenesis in Staphylococus aureus, Streptococcus pneumoniae, and Haemophilus influenzae.

Solithromycin Inhibition of Protein Synthesis and Ribosome Biogenesis in Staphylococus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Antimicrob Agents Chemother. 2013 Jan 14; Authors: Rodgers W, Frazier AD, Champney WS Abstract 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 IC(50) 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 IC(50) 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 IC(50) concentration of solithromycin. Turnover of 23S rRNA was stimul...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research