Extended-spectrum AmpC cephalosporinase in Acinetobacter baumannii: ADC-56 confers resistance to cefepime

Antimicrob Agents Chemother. 2011 Oct;55(10):4922-5. doi: 10.1128/AAC.00704-11. Epub 2011 Jul 25.

Abstract

ADC-56, a novel extended-spectrum AmpC (ESAC) β-lactamase, was identified in an Acinetobacter baumannii clinical isolate. ADC-56 possessed an R148Q change compared with its putative progenitor, ADC-30, which enabled it to hydrolyze cefepime. Molecular modeling suggested that R148 interacted with Q267, E272, and I291 through a hydrogen bond network which constrained the H-10 helix. This permitted cefepime to undergo conformational changes in the active site, with the carboxyl interacting with R340, likely allowing for better binding and turnover.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / enzymology*
  • Acinetobacter baumannii / genetics
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Cefepime
  • Cephalosporin Resistance / genetics
  • Cephalosporinase / chemistry
  • Cephalosporinase / genetics
  • Cephalosporinase / metabolism*
  • Cephalosporins / pharmacology*
  • Drug Resistance, Bacterial
  • Genes, Bacterial
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cephalosporins
  • Cefepime
  • Cephalosporinase
  • AmpC beta-lactamases
  • beta-Lactamases

Associated data

  • GDB/JF265067
  • GENBANK/JF265068