LSTM Home > LSTM Research > LSTM Online Archive

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

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

s41467-020-18668-2.pdf - Published Version
Available under License Creative Commons Attribution.

Download (759kB) | Preview


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):
Depositing User: Cathy Waldron
Date Deposited: 03 Oct 2020 11:04
Last Modified: 03 Oct 2020 11:04


View details

Actions (login required)

Edit Item Edit Item