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Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance

Thibault Stalder, Linda M. Rogers, Chris Renfrow, Hirokazu Yano, Zachary Smith, Eva M. Top
doi: https://doi.org/10.1101/146118
Thibault Stalder
1Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA
2Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho, USA
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Linda M. Rogers
1Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA
2Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho, USA
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Chris Renfrow
1Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA
2Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho, USA
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Hirokazu Yano
1Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA
2Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho, USA
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Zachary Smith
1Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA
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Eva M. Top
1Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA
2Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho, USA
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  • For correspondence: evatop@uidaho.edu
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ABSTRACT

Multidrug resistant bacterial pathogens have become a serious global human health threat, and conjugative plasmids are important drivers of the rapid spread of resistance to last-resort antibiotics. Whereas antibiotics have been shown to select for adaptation of resistance plasmids to their new bacterial hosts, or vice versa, a general evolutionary mechanism has not yet emerged. Here we conducted an experimental evolution study aimed at determining general patterns of plasmid-bacteria evolution. Specifically, we found that a large conjugative resistance plasmid follows the same evolutionary trajectories as its non-conjugative mini-replicon in the same and other species. Furthermore, within a single host–plasmid pair three distinct patterns of adaptive evolution led to increased plasmid persistence: i) mutations in the replication protein gene (trfA1); ii) the acquisition by the resistance plasmid of a transposon from a co-residing plasmid encoding a putative toxin-antitoxin system; iii) a mutation in the host’s global transcriptional regulator gene fur. Since each of these evolutionary solutions individually have been shown to increase plasmid persistence in other plasmid-host pairs, our work points towards common mechanisms of plasmid stabilization. These could become the targets of future alternative drug therapies to slow down the spread of antibiotic resistance.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 05, 2017.
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Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance
Thibault Stalder, Linda M. Rogers, Chris Renfrow, Hirokazu Yano, Zachary Smith, Eva M. Top
bioRxiv 146118; doi: https://doi.org/10.1101/146118
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Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance
Thibault Stalder, Linda M. Rogers, Chris Renfrow, Hirokazu Yano, Zachary Smith, Eva M. Top
bioRxiv 146118; doi: https://doi.org/10.1101/146118

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