Piperacillin/tazobactam resistance in a clinical isolate of <i>Escherichia coli</i> due to IS<i>26</i>-mediated amplification of <i>bla</i><sub>TEM-1B</sub>

Hubbard, Alasdair TM, Mason, Jenifer, Roberts, Paul, Parry, Christopher M ORCID: 0000-0001-7563-7282, Corless, Caroline, van Aartsen, Jon, Howard, Alex ORCID: 0000-0002-4195-6821, Bulgasim, Issra, Fraser, Alice J, Adams, Emily R
et al (show 2 more authors) (2020) Piperacillin/tazobactam resistance in a clinical isolate of <i>Escherichia coli</i> due to IS<i>26</i>-mediated amplification of <i>bla</i><sub>TEM-1B</sub>. NATURE COMMUNICATIONS, 11 (1). 4915-.

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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 bla<sub>TEM-1B</sub>. The TU re-inserts into the chromosome adjacent to IS26 and forms a tandem array of TUs, which increases the copy number of bla<sub>TEM-1B,</sub> leading to TEM-1B hyperproduction and TZP resistance. Despite a significant increase in bla<sub>TEM-1B</sub> copy number, the TZP-resistant isolate does not incur a fitness cost compared to the TZP-susceptible ancestor. This mechanism of amplification of bla<sub>TEM-1B</sub> is an important consideration when using genomic data to predict susceptibility to TZP.

Item Type: Article
Uncontrolled Keywords: Chromosomes, Bacterial, Humans, Escherichia coli, Escherichia coli Infections, Piperacillin, beta-Lactamases, Escherichia coli Proteins, DNA, Bacterial, DNA Transposable Elements, RNA, Ribosomal, 16S, Anti-Bacterial Agents, Drug Therapy, Combination, Microbial Sensitivity Tests, Drug Resistance, Multiple, Bacterial, Gene Amplification, Gene Expression Regulation, Bacterial, Polymorphism, Restriction Fragment Length, Genome, Bacterial, Whole Genome Sequencing, Tazobactam
Depositing User: Symplectic Admin
Date Deposited: 24 Sep 2020 09:56
Last Modified: 14 Oct 2023 20:25
DOI: 10.1038/s41467-020-18668-2
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3102326