Related Experiment Videos
Macrolide antibiotics inhibit 50S ribosomal subunit assembly in Bacillus subtilis and Staphylococcus aureus
1Department of Biochemistry, J. H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA.
Abstract:
Macrolide antibiotics are clinically important antibiotics which are effective inhibitors of protein biosynthesis in bacterial cells. We have recently shown that some of these compounds also inhibit 50S ribosomal subunit formation in Escherichia coli. Now we show that certain macrolides have the same effect in two gram-positive organisms, Bacillus subtilis and Staphylococcus aureus. Assembly in B. subtilis was prevented by erythromycin, clarithromycin, and azithromycin but not by oleandomycin. 50S subunit formation in S. aureus was prevented by each of seven structurally related 14-membered macrolides but not by lincomycin or two streptogramin antibiotics. Erythromycin treatment did not stimulate the breakdown of performed 50S subunits in either organism. The formation of the 30S ribosomal subunit was also unaffected by these compounds. Assembly was also inhibited in a B. subtilis strain carrying a plasmid with the ermC gene that confers macrolide resistance by rRNA methylation. These results suggest that ribosomes contain an additional site for the inhibitory functions of macrolide antibiotics.
Insights
Certain macrolide antibiotics inhibit bacterial protein synthesis by preventing the formation of 50S ribosomal subunits in gram-positive bacteria like Bacillus subtilis and Staphylococcus aureus. This suggests an additional antibiotic binding site on bacterial ribosomes.
Area of Science:
- Microbiology
- Molecular Biology
- Antibiotic Resistance
Background:
- Macrolide antibiotics are crucial for inhibiting bacterial protein biosynthesis.
- Previous research indicated macrolides inhibit 50S ribosomal subunit formation in Escherichia coli.
Purpose of the Study:
- To investigate the effect of macrolide antibiotics on 50S ribosomal subunit formation in gram-positive bacteria.
- To determine if macrolides inhibit ribosomal subunit assembly in Bacillus subtilis and Staphylococcus aureus.
Main Methods:
- Treatment of Bacillus subtilis and Staphylococcus aureus with various macrolide antibiotics.
- Assessment of 50S ribosomal subunit formation and 30S subunit stability.
- Analysis of macrolide resistance mechanisms in a B. subtilis strain.
Main Results:
- Erythromycin, clarithromycin, and azithromycin inhibited 50S subunit assembly in B. subtilis.
- Seven 14-membered macrolides prevented 50S subunit formation in S. aureus.
- Macrolides did not affect pre-formed 50S subunits or 30S subunit formation.
- Inhibition occurred even in a macrolide-resistant B. subtilis strain.
Conclusions:
- Macrolide antibiotics inhibit 50S ribosomal subunit assembly in gram-positive bacteria.
- These findings suggest the presence of an additional inhibitory site for macrolides on bacterial ribosomes.