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

Matthew J. Ellington; D. M. Livermore; T. L. Pitt; L. M.C. Hall; N. Woodford

doi:10.1111/j.1469-0691.2006.01424.x

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

Matthew J. Ellington^*, D. M. Livermore, T. L. Pitt, L. M.C. Hall, N. Woodford

^*Corresponding author for this work

ARMHAI Reference Lab

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

TEM-1 and TEM_pUC19 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 bla_TEM-1 and bla_TEM-pUC19 genes, conferring the Arg164His amino-acid substitution found in the TEM-29 ESBL. Non-ESBL mutants lacked changes in bla_TEM.

Original language	English
Pages (from-to)	800-803
Number of pages	4
Journal	Clinical Microbiology and Infection
Volume	12
Issue number	8
DOIs	https://doi.org/10.1111/j.1469-0691.2006.01424.x
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/j.1469-0691.2006.01424.x

Cite this

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

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.",

keywords = "Bla, Ceftazidime, Escherichia coli, Extended-spectrum β-lactamase, Hyper-mutator, Resistance",

author = "Ellington, {Matthew J.} and Livermore, {D. M.} and Pitt, {T. L.} and Hall, {L. M.C.} and N. Woodford",

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).",

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AU - Ellington, Matthew J.

AU - Livermore, D. M.

AU - Pitt, T. L.

AU - Hall, L. M.C.

AU - Woodford, N.

N1 - 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).

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N2 - 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.

AB - 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.

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KW - Resistance

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ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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