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

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Authors
Hubbard, ATM
Mason, J
Roberts, Paul cc
Parry, CM
Corless, C
van Aartsen, J
Howard, A
Bulgasim, I
Fraser, AJ
Adams, ER
Issue Date
2020-10-01

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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.
Citation
Hubbard, A.T.M., Mason, J., Roberts, P. et al. (2020) Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B. Nature Communications 11, 4915 (2020). https://doi.org/10.1038/s41467-020-18668-2
Publisher
Springer
Journal
Nature Communications
URI
http://hdl.handle.net/2436/624708
DOI
10.1038/s41467-020-18668-2
PubMed ID
33004811 (pubmed)
Type
Journal article
Language
en
Description
© 2020 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/s41467-020-18668-2
ISSN
2041-1723
EISSN
2041-1723
Sponsors
This work was supported by the Liverpool School of Tropical Medicine Director’s Catalyst Fund awarded to A.T.M.H. and T.E. A.P.R. would like to acknowledge funding from the AMR Cross-Council Initiative through a grant from the Medical Research Council, a Council of UK Research and Innovation (Grant number; MR/S004793/1), and funding from the National Institute for Health Research. (Grant Number; NIHR200632).
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Licence for published version: Creative Commons Attribution 4.0 International
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International