000 | 02871 am a22003373u 4500 | ||
---|---|---|---|
042 | _adc | ||
100 | 1 | 0 |
_aDelaFuente, Javier _eauthor _91690 |
700 | 1 | 0 |
_aToribio-Celestino, Laura _eauthor _91691 |
700 | 1 | 0 |
_aSantos-Lopez, Alfonso _eauthor _91692 |
700 | 1 | 0 |
_aLeón-Sampedro, Ricardo _eauthor _91693 |
700 | 1 | 0 |
_aValle, Aida Alonso-del _eauthor _91694 |
700 | 1 | 0 |
_aCostas, Coloma _eauthor _91695 |
700 | 1 | 0 |
_aHernández-García, Marta _eauthor _91696 |
700 | 1 | 0 |
_aCui, Lun _eauthor _91697 |
700 | 1 | 0 |
_aRodríguez-Beltrán, Jerónimo _eauthor _91698 |
700 | 1 | 0 |
_aBikard, David _eauthor _91699 |
700 | 1 | 0 |
_aCantón, Rafael _eauthor _91700 |
700 | 1 | 0 |
_aMillan, Alvaro San _eauthor _91701 |
245 | 0 | 0 | _aWithin-patient evolution of plasmid-mediated antimicrobial resistance |
260 | _c2022-10-27. | ||
500 | _a/pmc/articles/PMC7613874/ | ||
500 | _a/pubmed/36303001 | ||
520 | _aAntimicrobial 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. | ||
540 | _a | ||
540 | _ahttps://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 | ||
546 | _aen | ||
690 | _aArticle | ||
655 | 7 |
_aText _2local |
|
786 | 0 | _nNat Ecol Evol | |
856 | 4 | 1 |
_uhttp://dx.doi.org/10.1038/s41559-022-01908-7 _zConnect to this object online. |
999 |
_c2014 _d2014 |