Susceptibility to beta-lactam antibiotics of Pseudomonas aeruginosa overproducing penicillin-binding protein 3.
By using a broad-host-range vector, pUCP27, the Pseudomonas aeruginosa and Escherichia coli pbpB genes, which encode penicillin-binding protein 3 (PBP3), were separately overexpressed in a P. aeruginosa strain, PAO4089, that is deficient in producing chromosomal beta-lactamase. Susceptibility studies indicated that overproduction of the P. aeruginosa PBP3 in PAO4089 resulted in twofold-increased resistance to aztreonam, fourfold-increased resistance to cefepime and cefsulodin, and eightfold-increased resistance to ceftazidime, whereas overproduction of the P. aeruginosa PBP3 in PAO4089 did not affect susceptibility to PBP1-targeted cephaloridine or PBP2-targeted imipenem. Similar results were obtained with PAO4089 overproducing E. coli PBP3, with the exception that there was no influence on the MICs or minimal bactericidal concentrations of cefsulodin and cefepime, which have very low affinities for E. coli PBP3. These data are consistent with the conclusion that PBP3 has to achieve a certain level of saturation, with beta-lactams targeted to this protein, to result in cell inhibition or death.
Liao
X
X
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Hancock
R E
RE
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D029968:Escherichia coli Proteins; D006602:Hexosyltransferases / Q000096:biosynthesis* / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009097:Multienzyme Complexes / Q000096:biosynthesis* / Q000187:drug effects; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D046928:Peptidoglycan Glycosyltransferase; D010458:Peptidyl Transferases / Q000096:biosynthesis* / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D029968:Escherichia coli Proteins; C478704:FtsI protein, E coli; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D046928:Peptidoglycan Glycosyltransferase; D002267:Muramoylpentapeptide Carboxypeptidase