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Nat Commun. 2014 Oct 10;5:5208. doi: 10.1038/ncomms6208.

Positive selection and compensatory adaptation interact to stabilize non-transmissible plasmids.

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Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
1] Department of Zoology, University of Oxford, Oxford OX1 3PS, UK [2] Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca 62210, México.
1] Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7BN, UK [2] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.


Plasmids are important drivers of bacterial evolution, but it is challenging to understand how plasmids persist over the long term because plasmid carriage is costly. Classical models predict that horizontal transfer is necessary for plasmid persistence, but recent work shows that almost half of plasmids are non-transmissible. Here we use a combination of mathematical modelling and experimental evolution to investigate how a costly, non-transmissible plasmid, pNUK73, can be maintained in populations of Pseudomonas aeruginosa. Compensatory adaptation increases plasmid stability by eliminating the cost of plasmid carriage. However, positive selection for plasmid-encoded antibiotic resistance is required to maintain the plasmid by offsetting reductions in plasmid frequency due to segregational loss. Crucially, we show that compensatory adaptation and positive selection reinforce each other's effects. Our study provides a new understanding of how plasmids persist in bacterial populations, and it helps to explain why resistance can be maintained after antibiotic use is stopped.

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