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

Hubbard ATM., Mason J., Roberts P., Parry CM., Corless C., van Aartsen J., Howard A., Bulgasim I., Fraser AJ., Adams ER., Roberts AP., Edwards T.

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.

More information Original publication

DOI

10.1038/s41467-020-18668-2

Type

Journal article

Publication Date

2020-10-01T00:00:00+00:00

Volume

11

Addresses

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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