Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene.
Spontaneous cefsulodin-resistant mutants of Pseudomonas aeruginosa PAO4089 were isolated on agar impregnated with 3 mg/l of cefsulodin. This strain does not produce any chromosomal beta-lactamase. The MICs of cefsulodin for the parent and its mutants were 0.78 and 12.5 mg/l, respectively. Complete cross-resistance between cefsulodin and seven other antipseudomonal beta-lactams was noted in the mutants. The mutant gene, designated as pbpB, was mapped by FP5 plasmid-mediated conjugation and found to be near to cys-59 on the PAO chromosome, the gene order being pur-67, oruI, pbpB and cys-59. There were no detectable differences between the parent and its mutants in their outer membrane protein profiles. Penicillin-binding protein assay, by the competition method, with cefsulodin or carbenicillin showed a significant reduction in affinity of PBP3 for these beta-lactams. This PBP is the primary target for cefsulodin in P. aeruginosa. The genetic mechanism by which the cefsulodin-resistant clinical isolates of P. aeruginosa have emerged is discussed.
Gotoh
N
N
Department of Microbiology, Kyoto Pharmaceutical University, Japan.
Nunomura
K
K
Nishino
T
T
D000217:Acyltransferases / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000302:isolation & purification; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics*; D002352:Carrier Proteins; D002441:Cefsulodin / Q000494:pharmacology*; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D003433:Crosses, Genetic; D004352:Drug Resistance, Microbial / Q000235:genetics; D006602:Hexosyltransferases / Q000032:analysis / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D009097:Multienzyme Complexes / Q000032:analysis / Q000235:genetics*; D002267:Muramoylpentapeptide Carboxypeptidase; D009154:Mutation; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000032:analysis / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D001618:beta-Lactamases / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D000217:Acyltransferases; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; D002441:Cefsulodin