Rearrangement of a large novel Pseudomonas aeruginosa gene island in strains isolated from a patient developing ventilator-associated pneumonia

J Clin Microbiol. 2014 Jul;52(7):2430-8. doi: 10.1128/JCM.01626-13. Epub 2014 Apr 30.

Abstract

Bacterial gene islands add to the genetic repertoire of opportunistic pathogens. Here, we perform comparative analyses of three Pseudomonas aeruginosa strains isolated sequentially over a 3-week period from a patient with ventilator-associated pneumonia (VAP) who received clindamycin and piperacillin-tazobactam as part of their treatment regime. While all three strains appeared to be clonal by standard pulsed-field gel electrophoresis, whole-genome sequencing revealed subtle alterations in the chromosomal organization of the last two strains; specifically, an inversion event within a novel 124-kb gene island (PAGI 12) composed of 137 open reading frames [ORFs]. Predicted ORFs in the island included metabolism and virulence genes. Overexpression of a gene island-borne putative β-lactamase gene was observed following piperacillin-tazobactam exposure and only in those strains that had undergone the inversion event, indicating altered gene regulation following genomic remodeling. Examination of a separate cohort of 76 patients with VAP for integration at this tRNA(lys) recombination site demonstrated that patients exhibiting evidence of integration at this site had significantly higher 28-day mortality. These findings provide evidence that P. aeruginosa can integrate, rapidly remodel, and express exogenous genes, which likely contributes to its fitness in a clinical setting.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Clindamycin / therapeutic use
  • DNA, Bacterial / genetics
  • Electrophoresis, Gel, Pulsed-Field
  • Gene Rearrangement*
  • Genetic Variation*
  • Genome, Bacterial
  • Genomic Islands*
  • Humans
  • Longitudinal Studies
  • Molecular Typing
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / therapeutic use
  • Piperacillin / therapeutic use
  • Piperacillin, Tazobactam Drug Combination
  • Pneumonia, Ventilator-Associated / drug therapy
  • Pneumonia, Ventilator-Associated / microbiology*
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology*
  • Pseudomonas aeruginosa / classification*
  • Pseudomonas aeruginosa / genetics*
  • Pseudomonas aeruginosa / isolation & purification
  • Sequence Analysis, DNA

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Piperacillin, Tazobactam Drug Combination
  • Clindamycin
  • Penicillanic Acid
  • Piperacillin