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Labile 50S ribosome from partial macrolide-resistant Staphylococcus aureus
1Division of Microbiology, Hokkaido Institute of Pharmaceutical Sciences, Japan.
Abstract:
Staphylococcus aureus S704 and 8325MMT7 show constitutive resistance to macrolide antibiotics such as erythromycin (EM), oleandomycin, spiramycin, rosamicin and josamycin, except for tylosin, rokitamycin (RKM), and mycinamicin as well as lincosamide and streptogramin type B antibiotics (PM-resistance). Whenever 70S ribosomes from either of them were dissociated into 30S and 50S subunits in a 10-28%(W/W) linear sucrose gradient, the latter subunit was further cleaved into two small apparently equal particles (about 40S). RKM could no longer bind to either of the small particles. A prior exposure of 8325MMT7's 50S subunit to RKM (except EM) did not cause cleavage in any small particles. The largest component (M.W. 33.0kDa) of 50S ribosomal proteins was absent in at least the small particles. The first finding suggests that the lability of the 50S ribosome may be responsible for PM-resistance.
Insights
Staphylococcus aureus exhibits macrolide-lincosamide-streptogramin B resistance due to a labile 50S ribosomal subunit. This subunit cleaves into smaller particles, preventing rokitamycin binding and conferring resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Antibiotic Resistance
Background:
- Staphylococcus aureus strains S704 and 8325MMT7 display inherent resistance to macrolide antibiotics.
- This resistance, termed PM-resistance, extends to lincosamide and streptogramin B antibiotics but not all macrolides.
Purpose of the Study:
- To investigate the ribosomal basis of PM-resistance in Staphylococcus aureus.
- To determine the role of ribosomal subunits in antibiotic resistance.
Main Methods:
- Dissociation of 70S ribosomes into 30S and 50S subunits using sucrose gradient centrifugation.
- Analysis of subunit stability and antibiotic binding.
- Identification of ribosomal protein components.
Main Results:
- The 50S ribosomal subunit from resistant strains was unstable and cleaved into smaller particles (approx. 40S).
- Rokitamycin (RKM) failed to bind to these smaller particles.
- A specific 33.0kDa protein component was absent in the cleaved 50S subunit particles.
Conclusions:
- The lability and subsequent cleavage of the 50S ribosomal subunit is a key factor in Staphylococcus aureus's PM-resistance.
- This structural alteration of the ribosome prevents effective antibiotic binding, leading to resistance.