Inhibitor-sensitive AmpC β-lactamase variant produced by an Escherichia coli clinical isolate resistant to oxyiminocephalosporins and cephamycins

Yohei Doi, Jun Ichi Wachino, Masaji Ishiguro, Hiroshi Kurokawa, Kunikazu Yamane, Naohiro Shibata, Keigo Shibayama, Keiko Yokoyama, Haru Kato, Tetsuya Yagi, Yoshichika Arakawa

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Abstract

Escherichia coli HKY28, a ceftazidime-resistant strain isolated from a urine specimen in Japan, produced an inhibitor-sensitive AmpC β-lactamase variant. The deduced amino acid sequence of the enzyme contained a number of substitutions and a tripeptide deletion (Gly286-Ser287-Asp288) compared with the sequence of native AmpC of E. coli. When the deletion was reverted by a 9-base insertion at the relevant site of ampC in the clone, the typical inhibitor-resistant phenotype of AmpC was restored, while at the same time the levels of resistance to ceftazidime, cefpirome, and cefepime were reduced eightfold or more. Molecular modeling studies indicated that a structural change took place in the H-10 helix as a result of the deletion, and this change caused an alteration of the substrate binding site, leading to a unique phenotype analogous to that of inhibitor-sensitive class A extended-spectrum β-lactamases. The degree of inhibition was greater with sulbactam and tazobactam than with clavulanic acid. To our knowledge, this is the first report to have characterized an E. coli ampC that encodes chromosomal AmpC β-lactamase sensitive to the available β-lactamase inhibitors.

Original languageEnglish
Pages (from-to)2652-2658
Number of pages7
JournalAntimicrobial agents and chemotherapy
Volume48
Issue number7
DOIs
Publication statusPublished - 01-07-2004

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Doi, Y., Wachino, J. I., Ishiguro, M., Kurokawa, H., Yamane, K., Shibata, N., Shibayama, K., Yokoyama, K., Kato, H., Yagi, T., & Arakawa, Y. (2004). Inhibitor-sensitive AmpC β-lactamase variant produced by an Escherichia coli clinical isolate resistant to oxyiminocephalosporins and cephamycins. Antimicrobial agents and chemotherapy, 48(7), 2652-2658. https://doi.org/10.1128/AAC.48.7.2652-2658.2004