Evolutionary paths that expand plasmid host-range: Implications for spread of antibiotic resistance

Wesley Loftie-Eaton, Hirokazu Yano, Stephen Burleigh, Ryan S. Simmons, Julie M. Hughes, Linda M. Rogers, Samuel S. Hunter, Matthew L. Settles, Larry J. Forney, José M. Ponciano, Eva M. Top

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)


The World Health Organization has declared the emergence of antibiotic resistance to be a global threat to human health. Broad-host-range plasmids have a key role in causing this health crisis because they transfer multiple resistance genes to a wide range of bacteria. To limit the spread of antibiotic resistance, we need to gain insight into themechanisms by which the host range of plasmids evolves. Although initially unstable plasmids have been shown to improve their persistence through evolution of the plasmid, the host, or both, the means by which this occurs are poorly understood. Here, we sought to identify the underlying genetic basis of expanded plasmid host-range and increased persistence of an antibiotic resistance plasmid using a combined experimental-modeling approach that included whole-genome resequencing, molecular genetics and a plasmid population dynamics model. In nine of the ten previously evolved clones, changes in host and plasmid each slightly improved plasmid persistence, but their combination resulted in a much larger improvement, which indicated positive epistasis. The only genetic change in the plasmid was the acquisition of a transposable element from a plasmid native to the Pseudomonas host used in these studies. The analysis of genetic deletions showed that the critical genes on this transposon encode a putative toxin- Antitoxin (TA) and a cointegrate resolution system. As evolved plasmids were able to persist longer in multiple naive hosts, acquisition of this transposon also expanded the plasmid's host range, which has important implications for the spread of antibiotic resistance.

Original languageEnglish
Pages (from-to)885-897
Number of pages13
JournalMolecular biology and evolution
Issue number4
Publication statusPublished - 2016 Apr 1
Externally publishedYes


  • Antibiotic resistance
  • Broad host range plasmid
  • Epistasis
  • Experimental evolution
  • Horizontal gene transfer
  • Pseudomonas
  • Resolvase
  • Toxin- Antitoxin
  • Transposon

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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