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

Hubbard, Alasdair ORCID: https://orcid.org/0000-0001-6668-9179, Mason, Jenifer, Roberts, Paul, Parry, Christopher, Corless, Caroline, Aartsen, Jon van, Howard, Alex, Bulgasim, Issra, Fraser, Alice, Adams, Emily ORCID: https://orcid.org/0000-0002-0816-2835, Roberts, Adam ORCID: https://orcid.org/0000-0002-0760-3088 and Edwards, Thomas (2020) 'Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B'. Nature Communications, Vol 11, Issue 1, 4915..

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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 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.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Bacteria > QW 131 Gram-negative bacteria. WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 290 Escherichia coli infections
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/s41467-020-18668-2
Depositing User:	Cathy Waldron
Date Deposited:	03 Oct 2020 11:04
Last Modified:	03 Oct 2020 11:04
URI:	https://archive.lstmed.ac.uk/id/eprint/15543

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