Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B
Alasdair T. M. Hubbard, Jenifer Mason, Paul Roberts, Christopher M. Parry, Caroline Corless, J.J. van Aartsen, Alex Howard, Issra Bulgasim, Alice J. Fraser, Emily R. Adams, Adam P. Roberts, Thomas Edwards
Abstract
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 IS 26 -flanked pseudo-compound transposon, PTn 6762 , which harbours bla TEM-1B . The TU re-inserts into the chromosome adjacent to IS 26 and forms a tandem array of TUs, which increases the copy number of bla TEM-1B, leading to TEM-1B hyperproduction and TZP resistance. Despite a significant increase in bla TEM-1B copy number, the TZP-resistant isolate does not incur a fitness cost compared to the TZP-susceptible ancestor. This mechanism of amplification of bla TEM-1B is an important consideration when using genomic data to predict susceptibility to TZP.