Dimerization of plasmid DNA accelerates selection for antibiotic resistance

Authors

  • Alexander V. Mazin,

    Corresponding author
    1. Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Science, Lavrentjeva, 10, Novosibirsk 630090, Russia.
    • *For correspondence. E-mail avmazin@ucdavis.edu; Tel. (916) 752 9027; Fax (916) 752 9027;Fax(916) 752 9014.

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    • Section of Microbiology, University of California, Davis, California 95616–8665, USA

  • Tatiana V. Timchenko,

    1. Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Science, Lavrentjeva, 10, Novosibirsk 630090, Russia.
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    • Groupe d'Etude ‘Mutagenèse et Cancérogenèse’, Institut Curie, Bâtiment 110, Centre Universitaire, F-91405 Orsay, France

  • Murat K. Saparbaev,

    1. Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Science, Lavrentjeva, 10, Novosibirsk 630090, Russia.
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    • §

      Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555–1061, USA

  • Olga M. Mazina

    1. Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Science, Lavrentjeva, 10, Novosibirsk 630090, Russia.
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    • Section of Molecular and Cellular Biology, University of California, Davis, California 95616, USA.


Summary

Dimerization of multicopy plasmids is widely assumed to be disadvantageous both for plasmid maintenance and for the host cell. It is known that dimerization causes plasmid instability; dimer-containing cells grow slower than their monomer-containing counterparts. However, as we demonstrate here, under conditions of selective stress, dimers provide an advantage for bacteria. Dimers facilitate segregation of mutants from numerous copies of the parental plasmid. Accelerated segregation greatly increases the rate of accumulation of plasmids carrying mutations that are adaptive for bacteria. In contrast, resolution of dimers by site-specific recombination decreases, 103-105-fold, the efficiency of selection of spontaneous reversions in the tet gene of pBR327.

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