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Within-patient evolution of plasmid-mediated antimicrobial resistance (Record no. 1745)

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Personal name DelaFuente, Javier
Relator term author
9 (RLIN) 1690
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Title Within-patient evolution of plasmid-mediated antimicrobial resistance
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Date of publication, distribution, etc. 2022-10-27.
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General note /pmc/articles/PMC7613874/
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General note /pubmed/36303001
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Summary, etc. Antimicrobial resistance (AMR) in bacteria is a major threat to public health, and one of the key elements in the spread and evolution of AMR in clinical pathogens is the transfer of conjugative plasmids. The drivers of AMR evolution have been extensively studied in vitro, but the evolution of plasmid-mediated AMR in vivo remains poorly explored. Here, we tracked the evolution of the clinically-relevant plasmid pOXA-48, which confers resistance to the last-resort antibiotics carbapenems, in a large collection of enterobacterial clones isolated from the gut of hospitalised patients. Combining genomic and experimental approaches, we first characterized plasmid diversity and the genotypic and phenotypic effects of multiple plasmid mutations on a common genetic background. Second, using cutting-edge genomic editing in wild-type multidrug resistant enterobacteria, we dissected three cases of within-patient plasmid-mediated AMR evolution. Our results revealed compensatory evolution of plasmid-associated fitness cost, as well as the evolution of enhanced plasmid-mediated AMR, in bacteria evolving within the gut of hospitalised patients. Crucially, we observed that the evolution of pOXA-48-mediated AMR in vivo involves a pivotal trade-off between resistance levels and bacterial fitness. This study highlights the need to develop new evolution-informed approaches to tackle plasmid-mediated AMR dissemination.
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Terms governing use and reproduction
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Terms governing use and reproduction https://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
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Language note en
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Topical term or geographic name as entry element Article
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Genre/form data or focus term Text
Source of term local
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Toribio-Celestino, Laura
Relator term author
9 (RLIN) 1691
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Santos-Lopez, Alfonso
Relator term author
9 (RLIN) 1692
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name León-Sampedro, Ricardo
Relator term author
9 (RLIN) 1693
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Valle, Aida Alonso-del
Relator term author
9 (RLIN) 1694
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Costas, Coloma
Relator term author
9 (RLIN) 1695
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Hernández-García, Marta
Relator term author
9 (RLIN) 1696
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Cui, Lun
Relator term author
9 (RLIN) 1697
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Personal name Rodríguez-Beltrán, Jerónimo
Relator term author
9 (RLIN) 1698
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Bikard, David
Relator term author
9 (RLIN) 1699
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Personal name Cantón, Rafael
Relator term author
9 (RLIN) 1700
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Personal name Millan, Alvaro San
Relator term author
9 (RLIN) 1701
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Note Nat Ecol Evol
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Uniform Resource Identifier <a href="http://dx.doi.org/10.1038/s41559-022-01908-7">http://dx.doi.org/10.1038/s41559-022-01908-7</a>
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