Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of bla<sub>TEM-1B</sub>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33004811.
- Also identified by DOI 10.1038/s41467-020-18668-2 and PMC identifier 7530762.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 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.
Medical subject headings
- Anti-Bacterial Agents
- Drug Resistance, Multiple, Bacterial
- Escherichia coli
- Escherichia coli Infections
- Escherichia coli Proteins
- beta-Lactamases