title: Positive selection and compensatory adaptation interact to stabilize non-transmissible plasmids.
abstract: 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.
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: A
authors.initials: A
authors.lastname: San Millan
authors.affiliation: 1] Department of Zoology, University of Oxford, Oxford OX1 3PS, UK [2] Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca 62210, México.
authors.forename: R
authors.initials: R
authors.lastname: Peña-Miller
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: M
authors.initials: M
authors.lastname: Toll-Riera
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: Z V
authors.initials: ZV
authors.lastname: Halbert
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: McLean
authors.affiliation: 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.
authors.forename: B S
authors.initials: BS
authors.lastname: Cooper
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: MacLean
mesh_terms: D000222:Adaptation, Physiological; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D022761:Gene Transfer, Horizontal; D010957:Plasmids / Q000235:genetics* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents