黄色ブドウ球菌におけるマクロライド系抗生物質耐性に関する研究
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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[ ^<14>C]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.
- 公益社団法人日本薬学会の論文
- 2000-04-01
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関連論文
- 黄色ブドウ球菌におけるマクロライド排出遺伝子msrSAの発現機構の解析とその分子疫学
- 黄色ブドウ球菌におけるマクロライド系抗生物質耐性に関する研究
- マクロライド系薬剤の耐性機構--臨床分離細菌を中心に (あゆみ 薬剤耐性菌)
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- Characteristics and Localization of a Determinant Conferring Partial Macrolide Resistance in Staphylococcus aureus Carrying Plasmid