A mechanism of resistance to partial macrolide and streptogramin B antibiotics in Staphylococcus aureus clinically isolated in Hungary.
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 63kDa protein (MsrSA) present in the membrane from 8325(pEP2104) cells whose PMS-resistance was induced by a concentration of 1.35 micrograms 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 1 microgram 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 stain. 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.
Matsuoka
M
M
Department of Microbiology, Hokkaido Institute of Pharmaceutical Sciences, Japan.
Endou
K
K
Saitoh
S
S
Katoh
M
M
Nakajima
Y
Y
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004352:Drug Resistance, Microbial; D006801:Humans; D006814:Hungary; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010957:Plasmids; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D014769:Virginiamycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D014769:Virginiamycin