Genomics of adaptation during experimental evolution of the opportunistic pathogen Pseudomonas aeruginosa

PLoS Genet. 2012 Sep;8(9):e1002928. doi: 10.1371/journal.pgen.1002928. Epub 2012 Sep 13.

Abstract

Adaptation is likely to be an important determinant of the success of many pathogens, for example when colonizing a new host species, when challenged by antibiotic treatment, or in governing the establishment and progress of long-term chronic infection. Yet, the genomic basis of adaptation is poorly understood in general, and for pathogens in particular. We investigated the genetics of adaptation to cystic fibrosis-like culture conditions in the presence and absence of fluoroquinolone antibiotics using the opportunistic pathogen Pseudomonas aeruginosa. Whole-genome sequencing of experimentally evolved isolates revealed parallel evolution at a handful of known antibiotic resistance genes. While the level of antibiotic resistance was largely determined by these known resistance genes, the costs of resistance were instead attributable to a number of mutations that were specific to individual experimental isolates. Notably, stereotypical quinolone resistance mutations in DNA gyrase often co-occurred with other mutations that, together, conferred high levels of resistance but no consistent cost of resistance. This result may explain why these mutations are so prevalent in clinical quinolone-resistant isolates. In addition, genes involved in cyclic-di-GMP signalling were repeatedly mutated in populations evolved in viscous culture media, suggesting a shared mechanism of adaptation to this CF-like growth environment. Experimental evolutionary approaches to understanding pathogen adaptation should provide an important complement to studies of the evolution of clinical isolates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological / genetics*
  • Cell Culture Techniques
  • Ciprofloxacin / pharmacology
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / microbiology
  • DNA Gyrase / genetics*
  • Directed Molecular Evolution*
  • Drug Resistance, Microbial / drug effects
  • Drug Resistance, Microbial / genetics
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Mutation
  • Opportunistic Infections / genetics
  • Opportunistic Infections / microbiology
  • Pseudomonas aeruginosa / genetics*
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / pathogenicity

Substances

  • Ciprofloxacin
  • DNA Gyrase