Harvesting and amplifying gene cassettes confers cross-resistance to critically important antibiotics
2024; Public Library of Science; Volume: 20; Issue: 6 Linguagem: Inglês
10.1371/journal.ppat.1012235
ISSN1553-7374
AutoresPunyawee Dulyayangkul, Thomas Beavis, Winnie W. Y. Lee, Robbie Ardagh, Frances L. Edwards, Fergus Hamilton, Ian M. Head, Kate J. Heesom, Oliver Mounsey, Marek Murarik, Peechanika Pinweha, Carlos Reding, Naphat Satapoomin, John M. Shaw, Yuiko Takebayashi, Catherine L. Tooke, James Spencer, Philip B. Williams, Matthew B. Avison,
Tópico(s)Infections and bacterial resistance
ResumoAmikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the family Enterobacterales . Here we show that two gene cassettes located side-by-side in and ancestral integron similar to In 37 have been “harvested” by insertion sequence IS 26 as a transposon that is widely disseminated among the Enterobacterales . This transposon encodes the enzymes AAC(6’)-Ib-cr and OXA-1, reported, respectively, as amikacin and piperacillin/tazobactam resistance mechanisms. However, by studying bloodstream infection isolates from 769 patients from three hospitals serving a population of 1.2 million people in South West England, we show that increased enzyme production due to mutation in an IS 26 /In 37 -derived hybrid promoter or, more commonly, increased transposon copy number is required to simultaneously remove these two key therapeutic options; in many cases leaving only the last-resort antibiotic, meropenem. These findings may help improve the accuracy of predicting piperacillin/tazobactam treatment failure, allowing stratification of patients to receive meropenem or piperacillin/tazobactam, which may improve outcome and slow the emergence of meropenem resistance.
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