Evolved plasmid-host interactions reduce plasmid interference cost

Mol Microbiol. 2016 Sep;101(5):743-56. doi: 10.1111/mmi.13407. Epub 2016 Jun 15.


Antibiotic selection drives adaptation of antibiotic resistance plasmids to new bacterial hosts, but the molecular mechanisms are still poorly understood. We previously showed that a broad-host-range plasmid was poorly maintained in Shewanella oneidensis, but rapidly adapted through mutations in the replication initiation gene trfA1. Here we examined if these mutations reduced the fitness cost of TrfA1, and whether this was due to changes in interaction with the host's DNA helicase DnaB. The strains expressing evolved TrfA1 variants showed a higher growth rate than those expressing ancestral TrfA1. The evolved TrfA1 variants showed a lower affinity to the helicase than ancestral TrfA1 and were no longer able to activate the helicase at the oriV without host DnaA. Moreover, persistence of the ancestral plasmid was increased upon overexpression of DnaB. Finally, the evolved TrfA1 variants generated higher plasmid copy numbers than ancestral TrfA1. The findings suggest that ancestral plasmid instability can at least partly be explained by titration of DnaB by TrfA1. Thus under antibiotic selection resistance plasmids can adapt to a novel bacterial host through partial loss of function mutations that simultaneously increase plasmid copy number and decrease unfavorably high affinity to one of the hosts' essential proteins.

MeSH terms

  • DNA Helicases / metabolism
  • DNA Replication / genetics
  • DNA-Binding Proteins / metabolism
  • DnaB Helicases / genetics
  • DnaB Helicases / metabolism
  • Drug Resistance, Microbial
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli / virology
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Plasmids / genetics
  • Plasmids / metabolism*
  • Shewanella / genetics
  • Shewanella / virology*


  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • TrfA protein, E coli
  • DNA Helicases
  • DnaB Helicases