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Updated: Aug 9, 2026

Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
[Study of macrolide, lincosamide, and streptogramin B antibiotics resistance in Staphylococcus aureus]
1Division of Microbiology, Hokkaido College of Pharmacy, Japan.
Abstract:
Macrolide antibiotics (Mac) consist of a 12- to 16-membered lactone ring combined with a sugar moiety, and they inhibit protein synthesis via binding to 23S ribosomal RNA in bacteria. The 14- and 16-membered Mac are used for treating infectious diseases caused by Gram-positive and other bacteria; e.g., Haemophilus influenzae, Bordetella pertussis, Legionella pneumophila, Campylobacter, Treponema pallidum and Mycoplasma. Resistance to macrolide, lincosamide, and streptogramin-B (MLS) antibiotics in staphylococci is known to have the following mechanisms: 1) alteration of the target on ribosome due to dimethylation of a specific adenine residue in the 23S ribosomal RNA by the product of the erm gene, and consequently a decrease in binding of MLS antibiotics; 2) inactivation of streptogramin-B (STG-B) and lincosamide by the products of the sbh (encoding streptogramin B hydrolase) and linA' (encoding 3-lincomycin 4-clindamycin O-nucleotidyltransferase) genes, respectively; and 3) active efflux of Mac and STG-B antibiotics determined by the msrA and msrB genes in Staphylococcus epidermidis and Staphylococcus xylosus, respectively, both of which appear to act as an ATP-dependent efflux pump. I have shown that Staphylococcus aureus 8325(pEP2104) exhibits inducible resistance to PMS (partial macrolide and streptogramin B)-antibiotics [the 14-membered macrolides, erythromycin (EM), and oleandomycin (OL), and the 16-membered macrolide mycinamicin (MCM) and STG-B]. The sequence of the N-terminal amino acid residues of a 63 kDa protein (MsrSA) that appeared in the membrane of PMS-resistant strains was identical to that of an MsrA polypeptide related to enhanced efflux of [14C]EM. Ribosomes from PMS-resistant strains showed a similar affinity for EM to those from the PMS-sensitive host strain NCTC8325, and no inactivation of EM by 8325(pEP2104) was observed. In the present study, I showed the DNA sequence of the msrSA region on the constitutive PMS-resistant plasmid pMC38, PMS-inducible resistant plasmid pEP2104 and PMS-sensitive mutant plasmid pSP6, and the region that is essential for inducible expression in PMS resistance. In addition, I investigated the relationship between PMS resistance and intracellular accumulation of EM.
Insights
This study investigates macrolide antibiotic resistance in Staphylococcus aureus, identifying the msrSA gene region as crucial for inducible resistance. The findings reveal that this efflux pump mechanism, not target modification, is responsible for resistance to partial macrolide and streptogramin B antibiotics.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Macrolide antibiotics inhibit bacterial protein synthesis by targeting 23S ribosomal RNA.
- Antibiotic resistance mechanisms in staphylococci include target modification, drug inactivation, and active efflux.
- Previous work indicated inducible resistance to partial macrolide and streptogramin B (PMS) antibiotics in Staphylococcus aureus.
Purpose of the Study:
- To elucidate the genetic basis of inducible macrolide antibiotic resistance in Staphylococcus aureus.
- To characterize the msrSA gene region involved in PMS resistance.
- To investigate the relationship between PMS resistance and intracellular antibiotic accumulation.
Main Methods:
- DNA sequencing of the msrSA region on various plasmids (constitutive resistant, inducible resistant, sensitive mutant).
- Analysis of N-terminal amino acid sequences of membrane proteins in resistant strains.
- Investigation of erythromycin accumulation in resistant and sensitive strains.
Main Results:
- The msrSA gene region was sequenced, revealing its role in inducible PMS resistance.
- A 63 kDa protein (MsrSA) associated with enhanced efflux of erythromycin was identified.
- No evidence of target modification or drug inactivation was found; efflux appears to be the primary resistance mechanism.
Conclusions:
- The msrSA gene and its regulatory region are essential for inducible resistance to PMS antibiotics in Staphylococcus aureus.
- Active efflux, mediated by the MsrSA protein, is the primary mechanism of resistance.
- Understanding these mechanisms is critical for developing strategies to combat antibiotic resistance.
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Inhibitors of Gram-positive Cell Wall Synthesis
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