Alteration of PBP 3 entails resistance to imipenem in Listeria monocytogenes.
A mutant with decreased susceptibility to imipenem (IpR) was selected in vitro from a susceptible clinical isolate of Listeria monocytogenes (IpS). IpR exhibited decreased susceptibility to penicillin G (4 x MIC) and imipenem (16 x MIC) and increased susceptibility to cefotaxime (0.25 x MIC). Electrophoretic profiles of membrane proteins and penicillin-binding proteins (PBPs) were identical in the two strains; each strain had five PBPs with molecular masses of ca. 97, 83.3, 81, 77.1, and 42.6 kilodaltons. A decreased affinity of PBP 3 for penicillin G and imipenem (10-fold) was observed in IpR. In contrast, the affinity of PBP 3 for cefotaxime in IpR was increased twofold and correlated with the decreased MIC of this drug. From these findings and competition experiments with different beta-lactam antibiotics, we conclude that the alteration of PBP 3 is responsible for the decreased susceptibility of IpR to penicillin and imipenem and that PBP 3 might be an essential target of beta-lactam antibiotics in L. monocytogenes.
Pierre
J
J
Laboratoire de Microbiologie Medicale, Université Pierre et Marie Curie, Paris, France.
Boisivon
A
A
Gutmann
L
L
D000900:Anti-Bacterial Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002439:Cefotaxime / Q000378:metabolism; D002512:Cephalothin / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000502:physiology; D004586:Electrophoresis; D006602:Hexosyltransferases; D015378:Imipenem / Q000378:metabolism / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D009154:Mutation; D010400:Penicillin G / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D046915:Penicillin-Binding Proteins; D015378:Imipenem; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D002439:Cefotaxime; D010400:Penicillin G; D002512:Cephalothin