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

Alasdair T. M. Hubbard (), Jenifer Mason, Paul Roberts, Christopher M. Parry, Caroline Corless, Jon Aartsen, Alex Howard, Issra Bulgasim, Alice J. Fraser, Emily R. Adams, Adam P. Roberts and Thomas Edwards ()
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Alasdair T. M. Hubbard: Liverpool School of Tropical Medicine, Pembroke Place
Jenifer Mason: Liverpool University Hospital Foundation Trust
Paul Roberts: Liverpool University Hospital Foundation Trust
Christopher M. Parry: Alder Hey Children’s NHS Foundation Trust
Caroline Corless: Liverpool University Hospital Foundation Trust
Jon Aartsen: Liverpool University Hospital Foundation Trust
Alex Howard: Liverpool University Hospital Foundation Trust
Issra Bulgasim: Liverpool School of Tropical Medicine, Pembroke Place
Alice J. Fraser: Liverpool School of Tropical Medicine, Pembroke Place
Emily R. Adams: Liverpool School of Tropical Medicine, Pembroke Place
Adam P. Roberts: Liverpool School of Tropical Medicine, Pembroke Place
Thomas Edwards: Liverpool School of Tropical Medicine, Pembroke Place

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: 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 pseudo-compound transposon, PTn6762, 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.

Date: 2020
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DOI: 10.1038/s41467-020-18668-2

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