摘要：A plasmid pEP2104 originated from Staphylococcus aureus was clinically isolated in Hungary during 1977. The plasmid mediates inducible resistance to PMS-antibiotics ; partial macrolide [the 14-membered macrolides, erythromycin (EM) and oleandomycin and the 16-membered macrolides mycinamicin I (MCM I) and mycinamicin II (MCM II)] and type B streptogramin (MKM-B) antibiotics. The sequence of 31 amino acid residues obtained by N-terminal analysis of the 63 kDa protein (MsrSA) present in the membrane from 8325 (pEP2104) cells, whose PMS-resistance was induced by a concentration of 1.35 μg EM/ml [EM-induced 8325 (pEP2104)], was identical to the corresponding sequence in a membrane protein MsrA related to promoting efflux of [14C] EM [Ross J.I., et al., Mol. Microbiol., 4, 1207 (1990)]. A constitutive PMS-resistant strain 8325 (pMC38) was obtained from the 8325 (pEP2104) strain in the presence of 1μg MCMI/ml. No inactivation of EM in EM-induced 8325 (pEP2104) was observed. Moreover, poly (A)-directed polylysine synthesis by a cell-free system containing ribosomes from EM-induced 8325 (pEP2104) cells and S100 from Escherichia coli was inhibited by not only EM but spiramycin and MKM-B [Matsuoka M., et al., Biol. Pharm. Bull., 16, 1288 (1993)]. In addition, ribosomes from both EM-induced 8325 (pEP2104) and 8325 (pMC38) strains showed about the same affinity as those from the host strain, NCTC8325. These results suggest that, like MsrA protein, active drug-efflux due to MsrSA protein may be responsible for PMS-resistance. How can the 8325 (pMC38) strain discriminate PMS-antibiotics from most of 16-membered macrolides and lincosamides? A possible explanation is discussed in terms of the pKa-value related to the physicochemical nature of the antibiotics.
