Academic Journal
Harvesting and amplifying gene cassettes confers cross-resistance to critically important antibiotics
| العنوان: | Harvesting and amplifying gene cassettes confers cross-resistance to critically important antibiotics |
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| المؤلفون: | Dulyayangkul, Punyawee, Beavis, Thomas, Lee, Winnie W. Y., Ardagh, Robbie, Edwards, Frances, Hamilton, Fergus, Head, Ian, Heesom, Kate J., Mounsey, Oliver, Murarik, Marek, Pinweha, Peechanika, Reding, Carlos, Satapoomin, Naphat, Shaw, John M., Takebayashi, Yuiko, Tooke, Catherine L., Spencer, James, Williams, Philip B., Avison, Matthew B. |
| المساهمون: | Shafer, William M., Medical Research Council, Natural Environment Research Council, Llywodraeth Cymru, Medical Research Foundation, Wellcome Trust, Research Trainees Coordinating Centre, Royal Thai Government, University of Bristol |
| المصدر: | PLOS Pathogens ; volume 20, issue 6, page e1012235 ; ISSN 1553-7374 |
| بيانات النشر: | Public Library of Science (PLoS) |
| سنة النشر: | 2024 |
| المجموعة: | PLOS Publications (via CrossRef) |
| الوصف: | Amikacin 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1371/journal.ppat.1012235 |
| الاتاحة: | http://dx.doi.org/10.1371/journal.ppat.1012235 https://dx.plos.org/10.1371/journal.ppat.1012235 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.5C7BB33B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.ppat.1012235 |
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