Penicillin-binding protein 3 of Listeria monocytogenes as the primary lethal target for beta-lactams.
Penicillin-binding proteins (PBPs) of Listeria monocytogenes were detected by their ability to bind to [2,3-3H]benzylpenicillin. Five proteins with Mrs of 95,000, 84,000, 80,000, 76,000, and 49,000 were detected. PBPs 1 to 4 had a high affinity for [2,3-3H]benzylpenicillin and were relatively scarce (80 to 150 molecules per cell). In contrast, PBP 5 was more abundant (600 molecules per cell) but had a low affinity for [2,3-3H]benzylpenicillin. L. monocytogenes has a relatively high natural resistance to cephalosporins. Competition experiments showed that cephalosporins bound very poorly to PBP 3 but were good inhibitors of PBPs 1, 2, and 4, which were completely blocked at concentrations well below the MIC. Analysis of a spontaneous imipenem-resistant mutant revealed that resistance was likely due to an altered PBP 3 with a reduced affinity for [2,3-3H]benzylpenicillin. These results suggest that PBP 3 is a primary lethal target for beta-lactams in L. monocytogenes.
Vicente
M F
MF
Servicio de Microbiología, Hospital Ramon y Cajal, Madrid, Spain.
Pérez-Dáz
J C
JC
Baquero
F
F
Angel de Pedro
M
M
Berenguer
J
J
D000217:Acyltransferases / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002511:Cephalosporins / Q000494:pharmacology; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000187:drug effects / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002267:Muramoylpentapeptide Carboxypeptidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010400:Penicillin G / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D000217:Acyltransferases; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G