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Genetics. Dec 2003; 165(4): 1641–1649.
PMCID: PMC1462891

Amelioration of the cost of conjugative plasmid carriage in Eschericha coli K12.


Although plasmids can provide beneficial functions to their host bacteria, they might confer a physiological or energetic cost. This study examines how natural selection may reduce the cost of carrying conjugative plasmids with drug-resistance markers in the absence of antibiotic selection. We studied two plasmids, R1 and RP4, both of which carry multiple drug resistance genes and were shown to impose an initial fitness cost on Escherichia coli. To determine if and how the cost could be reduced, we subjected plasmid-containing bacteria to 1100 generations of evolution in batch cultures. Analysis of the evolved populations revealed that plasmid loss never occurred, but that the cost was reduced through genetic changes in both the plasmids and the bacteria. Changes in the plasmids were inferred by the demonstration that evolved plasmids no longer imposed a cost on their hosts when transferred to a plasmid-free clone of the ancestral E. coli. Changes in the bacteria were shown by the lowered cost when the ancestral plasmids were introduced into evolved bacteria that had been cured of their (evolved) plasmids. Additionally, changes in the bacteria were inferred because conjugative transfer rates of evolved R1 plasmids were lower in the evolved host than in the ancestral host. Our results suggest that once a conjugative bacterial plasmid has invaded a bacterial population it will remain even if the original selection is discontinued.

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Selected References

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  • Birnboim HC, Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. [PMC free article] [PubMed]
  • Björkman J, Hughes D, Andersson DI. Virulence of antibiotic-resistant Salmonella typhimurium. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3949–3953. [PMC free article] [PubMed]
  • Björkman J, Nagaev I, Berg OG, Hughes D, Andersson DI. Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance. Science. 2000 Feb 25;287(5457):1479–1482. [PubMed]
  • Bouma JE, Lenski RE. Evolution of a bacteria/plasmid association. Nature. 1988 Sep 22;335(6188):351–352. [PubMed]
  • Caulcott CA, Dunn A, Robertson HA, Cooper NS, Brown ME, Rhodes PM. Investigation of the effect of growth environment on the stability of low-copy-number plasmids in Escherichia coli. J Gen Microbiol. 1987 Jul;133(7):1881–1889. [PubMed]
  • Clerget M, Chandler M, Caro L. The structure of R1drd19: a revised physical map of the plasmid. Mol Gen Genet. 1981;181(2):183–191. [PubMed]
  • Noack D, Roth M, Geuther R, Müller G, Undisz K, Hoffmeier C, Gáspár S. Maintenance and genetic stability of vector plasmids pBR322 and pBR325 in Escherichia coli K12 strains grown in a chemostat. Mol Gen Genet. 1981;184(1):121–124. [PubMed]
  • Cooper NS, Brown ME, Caulcott CA. A mathematical method for analysing plasmid stability in micro-organisms. J Gen Microbiol. 1987 Jul;133(7):1871–1880. [PubMed]
  • Nordström K, Molin S, Aagaard-Hansen H. Partitioning of plasmid R1 in Escherichia coli. I. Kinetics of loss of plasmid derivatives deleted of the par region. Plasmid. 1980 Sep;4(2):215–227. [PubMed]
  • Dykhuizen DE, Hartl DL. Selection in chemostats. Microbiol Rev. 1983 Jun;47(2):150–168. [PMC free article] [PubMed]
  • Pansegrau W, Lanka E, Barth PT, Figurski DH, Guiney DG, Haas D, Helinski DR, Schwab H, Stanisich VA, Thomas CM. Complete nucleotide sequence of Birmingham IncP alpha plasmids. Compilation and comparative analysis. J Mol Biol. 1994 Jun 24;239(5):623–663. [PubMed]
  • Fang FC, Helinski DR. Broad-host-range properties of plasmid RK2: importance of overlapping genes encoding the plasmid replication initiation protein TrfA. J Bacteriol. 1991 Sep;173(18):5861–5868. [PMC free article] [PubMed]
  • Reynolds MG. Compensatory evolution in rifampin-resistant Escherichia coli. Genetics. 2000 Dec;156(4):1471–1481. [PMC free article] [PubMed]
  • Schmidhauser TJ, Helinski DR. Regions of broad-host-range plasmid RK2 involved in replication and stable maintenance in nine species of gram-negative bacteria. J Bacteriol. 1985 Oct;164(1):446–455. [PMC free article] [PubMed]
  • Godwin D, Slater JH. The influence of the growth environment on the stability of a drug resistance plasmid in Escherichia coli K12. J Gen Microbiol. 1979 Mar;111(1):201–210. [PubMed]
  • Helling RB, Kinney T, Adams J. The maintenance of Plasmid-containing organisms in populations of Escherichia coli. J Gen Microbiol. 1981 Mar;123(1):129–141. [PubMed]
  • Jensen RB, Grohmann E, Schwab H, Díaz-Orejas R, Gerdes K. Comparison of ccd of F, parDE of RP4, and parD of R1 using a novel conditional replication control system of plasmid R1. Mol Microbiol. 1995 Jul;17(2):211–220. [PubMed]
  • Strohmaier H, Noiges R, Kotschan S, Sawers G, Högenauer G, Zechner EL, Koraimann G. Signal transduction and bacterial conjugation: characterization of the role of ArcA in regulating conjugative transfer of the resistance plasmid R1. J Mol Biol. 1998 Mar 27;277(2):309–316. [PubMed]
  • Jones IM, Primrose SB, Robinson A, Ellwood DC. Maintenance of some ColE1-type plasmids in chemostat culture. Mol Gen Genet. 1980;180(3):579–584. [PubMed]
  • Valla S, Haugan K, Durland R, Helinski DR. Isolation and properties of temperature-sensitive mutants of the trfA gene of the broad host range plasmid RK2. Plasmid. 1991 Mar;25(2):131–136. [PubMed]
  • Lenski RE, Bouma JE. Effects of segregation and selection on instability of plasmid pACYC184 in Escherichia coli B. J Bacteriol. 1987 Nov;169(11):5314–5316. [PMC free article] [PubMed]
  • Zünd P, Lebek G. Generation time-prolonging R plasmids: correlation between increases in the generation time of Escherichia coli caused by R plasmids and their molecular size. Plasmid. 1980 Jan;3(1):65–69. [PubMed]

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