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

  • Loftie-Eaton W
  • Yano H
  • Burleigh S
 et al. 
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Abstract

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 the mechanisms by which the host range of plasmids evolves. While 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 re-sequencing, molecular genetics and a plasmid population dynamics model. In 9 of the 10 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. Since 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.

Author-supplied keywords

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

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Authors

  • Wesley Loftie-Eaton

  • Hirokazu Yano

  • Stephen Burleigh

  • Ryan S. Simmons

  • Julie M. Hughes

  • Linda M. Rogers

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