M. Matsuoka et al., A MECHANISM OF RESISTANCE TO PARTIAL MACROLIDE AND STREPTOGRAMIN-B ANTIBIOTICS IN STAPHYLOCOCCUS-AUREUS CLINICALLY ISOLATED IN HUNGARY, Biological & pharmaceutical bulletin, 18(11), 1995, pp. 1482-1486
A plasmid pEP2104 originated from Staphylococcus aureus was clinically
isolated in Hungary during 1977. The plasmid mediates inducible resis
tance to PMS-antibiotics; partial macrolide [the 14-membered macrolide
s, erythromycin (EM) and oleandomycin and the 16-membered macrolides m
ycinamicin I(MCM I) and mycinamicin II(MCM II)] and type B streptogram
in (MKM-B) antibiotics. The sequence of 31 amino acid residues obtaine
d by N-terminal analysis of the 63 kDa protein (MsrSA) present in tbe
membrane from 8325(pEP2104) cells, whose PMS-resistance was induced by
a concentration of 1.35 mu g EM/ml [EM-induced 8325(pEP2104)], was id
entical to the corresponding sequence in a membrane protein MsrA relat
ed to promoting efflux of [C-14]EM [Ross J. I., et al., Mol. Microbiol
., 4, 1207 (1990)]. A constitutive PMS-resistant strain 8325(pMC38) wa
s obtained from the 8325(pEP2104) strain in the presence of 1 mu g MCM
I/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) tells and S100 fro
m Escherichia coil was inhibited by not only EM but spiramycin and MKM
-B [Matsuoka M., et al., Biol. Pharm. Bull., 16, 1288 (1993)]. In addi
tion, ribosomes from both EM-induced 8325(pEP2104) and 8325(pMC38) str
ains showed about the same affinity as those from the host strain, NCT
C8325. These results suggest that, like MsrA protein, active drug-effl
ux due to MsrSA protein may be responsible for PMS-resistance. How can
the 8325(pMC38) strain discriminate PMS-antibiotics from most of 16-m
embered macrolides and lincosamides? A possible explanation is discuss
ed in terms of the pK(a)-value related to the physicochemical nature o
f the antibiotics.