TY - JOUR
T1 - Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B
AU - Hubbard, Alasdair
AU - Mason, Jenifer
AU - Roberts, Paul
AU - Parry, Christopher
AU - Corless, Caroline
AU - van Aartsen, Jon
AU - Howard, Alex
AU - Bulgasim, Issra
AU - Fraser, Alice
AU - Adams, Emily
AU - Roberts, Adam
AU - Edwards, Thomas
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-18668-2
DO - 10.1038/s41467-020-18668-2
M3 - Article
SN - 2041-1723
VL - 11
SP - 4915
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4915
ER -