Contribution of beta-lactamase and PBP amino acid substitutions to amoxicillin/clavulanate resistance in beta-lactamase-positive, amoxicillin/clavulanate-resistant Haemophilus influenzae.
The roles of beta-lactamase and alterations in penicillin-binding protein in the development of amoxicillin and amoxicillin/clavulanate resistance in two beta-lactamase-positive, amoxicillin/clavulanate-resistant (BLPACR) strains of Haemophilus influenzae were investigated. Seven beta-lactamase-negative, ampicillin-resistant (BLNAR) strains were also studied for comparison of their resistance mechanisms. All strains had been recovered from patients in Japan. The TEM type beta-lactamase of the two BLPACR strains had 100% homology with the amino acid sequences of published TEM-1 beta-lactamase, showing that amoxicillin/clavulanate resistance was not associated with mutations in this beta-lactamase. However, these strains, as well as the seven BLNAR strains, had multiple mutations in ftsI, which encodes penicillin binding protein 3 (PBP3). The transformation of H. influenzae Rd strain with amplified ftsI genes from two BLPACR and two BLNAR strains enabled the selection of amoxicillin/clavulanate-resistant transformants with the same mutations as their parent strains. We concluded that amoxicillin/clavulanate resistance in the two BLPACR strains was due to changes in PBP3. The possibility of the presence of an extended spectrum beta-lactamase was excluded in the BLPACR strains studied.
Matic
Vlatka
V
Department of Pathology, Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
Bozdogan
Bülent
B
Jacobs
Michael R
MR
Ubukata
Kimiko
K
Appelbaum
Peter C
PC
D019943:Amino Acid Substitution / Q000235:genetics*; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D006192:Haemophilus Infections / Q000382:microbiology; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000235:genetics*; D006602:Hexosyltransferases / Q000235:genetics* / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics / Q000502:physiology; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000235:genetics* / Q000378:metabolism*; D014169:Transformation, Bacterial; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D046915:Penicillin-Binding Proteins; D019980:Amoxicillin-Potassium Clavulanate Combination; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases