Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B

Alasdair Hubbard; Jenifer Mason; Paul Roberts; Christopher Parry; Caroline Corless; Jon van Aartsen; Alex Howard; Issra Bulgasim; Alice Fraser; Emily Adams; Adam Roberts; Thomas Edwards

doi:10.1038/s41467-020-18668-2

Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B

Alasdair Hubbard
, Jenifer Mason
, Paul Roberts
, Christopher Parry
, Caroline Corless
, Jon van Aartsen
, Alex Howard
, Issra Bulgasim
, Alice Fraser
, Emily Adams
, Adam Roberts
, Thomas Edwards

University of Liverpool
University of Wolverhampton
Alder Hey Children's NHS Foundation Trust
University of Nagasaki

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

66 Citations (Scopus)

Abstract

A phenotype of Escherichia coli and Klebsiella pneumoniae, resistant to piperacillin/tazobactam (TZP) but susceptible to carbapenems and 3rd generation cephalosporins, has emerged. The resistance mechanism associated with this phenotype has been identified as hyperproduction of the β-lactamase TEM. However, the mechanism of hyperproduction due to gene amplification is not well understood. Here we report a mechanism of gene amplification due to a translocatable unit (TU) excising from an IS26-flanked composite transposon, Tn6762, which harbours blaTEM-1B. The TU re-inserts into the chromosome adjacent to IS26 and forms a tandem array of TUs, which increases the copy number of blaTEM-1B, leading to TEM-1B hyperproduction and TZP resistance. Despite a significant increase in blaTEM-1B copy number, the TZP-resistant isolate does not incur a fitness cost compared to the TZP-susceptible ancestor. This mechanism of amplification of blaTEM-1B is an important consideration when using genomic data to predict susceptibility to TZP.

Original language	English
Article number	4915
Pages (from-to)	4915
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-18668-2
Publication status	Published - 1 Oct 2020

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Hubbard, A., Mason, J., Roberts, P., Parry, C., Corless, C., van Aartsen, J., Howard, A., Bulgasim, I., Fraser, A., Adams, E., Roberts, A., & Edwards, T. (2020). Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B. Nature Communications, 11(1), 4915. Article 4915. https://doi.org/10.1038/s41467-020-18668-2

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title = "Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B",

abstract = "A phenotype of Escherichia coli and Klebsiella pneumoniae, resistant to piperacillin/tazobactam (TZP) but susceptible to carbapenems and 3rd generation cephalosporins, has emerged. The resistance mechanism associated with this phenotype has been identified as hyperproduction of the β-lactamase TEM. However, the mechanism of hyperproduction due to gene amplification is not well understood. Here we report a mechanism of gene amplification due to a translocatable unit (TU) excising from an IS26-flanked composite transposon, Tn6762, which harbours blaTEM-1B. The TU re-inserts into the chromosome adjacent to IS26 and forms a tandem array of TUs, which increases the copy number of blaTEM-1B, leading to TEM-1B hyperproduction and TZP resistance. Despite a significant increase in blaTEM-1B copy number, the TZP-resistant isolate does not incur a fitness cost compared to the TZP-susceptible ancestor. This mechanism of amplification of blaTEM-1B is an important consideration when using genomic data to predict susceptibility to TZP.",

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Hubbard, A, Mason, J, Roberts, P, Parry, C, Corless, C, van Aartsen, J, Howard, A, Bulgasim, I, Fraser, A, Adams, E, Roberts, A & Edwards, T 2020, 'Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B', Nature Communications, vol. 11, no. 1, 4915, pp. 4915. https://doi.org/10.1038/s41467-020-18668-2

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AU - Hubbard, Alasdair

AU - Mason, Jenifer

AU - Roberts, Paul

AU - Parry, Christopher

AU - Corless, Caroline

AU - van Aartsen, Jon

AU - Howard, Alex

AU - Bulgasim, Issra

AU - Fraser, Alice

AU - Adams, Emily

AU - Roberts, Adam

AU - Edwards, Thomas

PY - 2020/10/1

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N2 - A phenotype of Escherichia coli and Klebsiella pneumoniae, resistant to piperacillin/tazobactam (TZP) but susceptible to carbapenems and 3rd generation cephalosporins, has emerged. The resistance mechanism associated with this phenotype has been identified as hyperproduction of the β-lactamase TEM. However, the mechanism of hyperproduction due to gene amplification is not well understood. Here we report a mechanism of gene amplification due to a translocatable unit (TU) excising from an IS26-flanked composite transposon, Tn6762, which harbours blaTEM-1B. The TU re-inserts into the chromosome adjacent to IS26 and forms a tandem array of TUs, which increases the copy number of blaTEM-1B, leading to TEM-1B hyperproduction and TZP resistance. Despite a significant increase in blaTEM-1B copy number, the TZP-resistant isolate does not incur a fitness cost compared to the TZP-susceptible ancestor. This mechanism of amplification of blaTEM-1B is an important consideration when using genomic data to predict susceptibility to TZP.

AB - A phenotype of Escherichia coli and Klebsiella pneumoniae, resistant to piperacillin/tazobactam (TZP) but susceptible to carbapenems and 3rd generation cephalosporins, has emerged. The resistance mechanism associated with this phenotype has been identified as hyperproduction of the β-lactamase TEM. However, the mechanism of hyperproduction due to gene amplification is not well understood. Here we report a mechanism of gene amplification due to a translocatable unit (TU) excising from an IS26-flanked composite transposon, Tn6762, which harbours blaTEM-1B. The TU re-inserts into the chromosome adjacent to IS26 and forms a tandem array of TUs, which increases the copy number of blaTEM-1B, leading to TEM-1B hyperproduction and TZP resistance. Despite a significant increase in blaTEM-1B copy number, the TZP-resistant isolate does not incur a fitness cost compared to the TZP-susceptible ancestor. This mechanism of amplification of blaTEM-1B is an important consideration when using genomic data to predict susceptibility to TZP.

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Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B

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