Development of extended-spectrum activity in TEM β-lactamases in hyper-mutable, mutS Escherichia coli

Matthew Ellington*, David Livermore, T. L. Pitt, L. M.C. Hall, Neil Woodford

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

TEM-1 and TEMpUC19 β-lactamases can gain activity against ceftazidime and other expanded-spectrum cephalosporins via point mutation. The frequency of emergent resistance to ceftazidime at 4 × MIC was elevated ≥250-fold in hyper-mutable, MutS-deficient Escherichia coli harbouring these β-lactamase genes on high- or low-copy plasmids. Moreover, although ceftazidime-resistant mutants, or those with reduced susceptibility, were selected in both the wild-type and mutS hosts, many more mutants in the mutS host showed ceftazidimase-type extended-spectrum β-lactamase (ESBL) activity. This correlated with a G-A point mutation at position 484 in the blaTEM-1 and blaTEM-pUC19 genes, conferring the Arg164His amino-acid substitution found in the TEM-29 ESBL. Non-ESBL mutants lacked changes in blaTEM.

Original languageEnglish
Pages (from-to)800-803
Number of pages4
JournalClinical Microbiology and Infection
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 2006

Bibliographical note

Funding Information:
The authors wish to thank R. Lloyd for the gift of E. coli strains, B. Bridges for discussions, and the UK Department of Health for financial support (grant no. 91 of the Resistance to Antibiotics and other Antimicrobial Agents Research Programme). This work was presented, in part, at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (Washington, DC, 2004) and the 15th European Congress of Clinical Microbiology and Infectious Diseases (Copenhagen, 2005).

Keywords

  • Bla
  • Ceftazidime
  • Escherichia coli
  • Extended-spectrum β-lactamase
  • Hyper-mutator
  • Resistance

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