Replacement of the essential penicillin-binding protein 5 by high-molecular mass PBPs may explain vancomycin-beta-lactam synergy in low-level vancomycin-resistant Enterococcus faecium D366.
The mechanism of synergy between vancomycin and penicillin, as well as other beta-lactam antibiotics, was examined in a penicillin-resistant E. faecium (D366) expressing an inducible low-level resistance to vancomycin. It was demonstrated that penicillin per se was not able to reduce the inducible expression of the 39.5-kDa protein (VANB) or the carboxypeptidase activity which are involved in the mechanism of vancomycin resistance of this strain. Assays of competition between 3H-benzylpenicillin and diverse beta-lactam antibiotics suggested as the most likely explanation of the synergy that, once vancomycin resistance has been induced, the high-molecular mass penicillin-binding proteins (PBPs), and possibly PBP1 in particular, which have a high affinity for beta-lactam antibiotics, take over the role of the low-affinity PBP5 which is, in the non-induced strain, responsible for beta-lactam resistance.
al-Obeid
S
S
Laboratoire de Microbiologie Médicale, Université Paris VI, France.
Billot-Klein
D
D
van Heijenoort
J
J
Collatz
E
E
Gutmann
L
L
D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D004347:Drug Interactions; D016984:Enterococcus faecium / Q000502:physiology*; D006602:Hexosyltransferases; D008565:Membrane Proteins / Q000032:analysis; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D010403:Penicillin Resistance / Q000502:physiology*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology*; D010458:Peptidyl Transferases; D014640:Vancomycin / Q000494:pharmacology*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D014640:Vancomycin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase