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Rapid genetic and phenotypic changes in Pseudomonas aeruginosa clinical strains during ventilator-associated

Elise Persyn1,2, Mohamed Sassi3, Marc Aubry4,5

  • 1EA3826 Université de Nantes, IRS2 Nantes Biotech, Nantes Cedex 1, F-44100, France. elise.thomas@chu-nantes.fr.

Scientific Reports
|March 20, 2019
PubMed

Insights

Antibiotic resistance in Pseudomonas aeruginosa during ventilator-associated pneumonia (VAP) is linked to changes in virulence. This study shows resistance evolution can alter bacterial virulence factors, even in short-term infections.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Genomics

Background:

  • Antibiotic treatment selects for resistant bacterial strains.
  • Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP).
  • The relationship between antibiotic resistance and virulence in P. aeruginosa VAP is not fully understood.

Purpose of the Study:

  • To investigate if the evolution of antibiotic resistance in P. aeruginosa during VAP is associated with changes in virulence.
  • To identify genetic modifications linked to resistance and virulence in P. aeruginosa isolates from VAP patients.

Main Methods:

  • Whole-genome sequencing of 12 P. aeruginosa isolates from four VAP patients with emerging resistance.
  • Analysis of virulence factors including quorum sensing, serum resistance, cytotoxicity, biofilm production, and twitching motility.
  • Identification of genetic mutations in resistance (ampD, mexR, oprD) and virulence/fitness genes (algB, gacA, groEL, lasR, mpl, pilE, pilM, rhlR).

Main Results:

  • Resistance development was attributed to genetic events in ampD, mexR, or oprD.
  • Associated genetic variations in virulence and fitness genes were observed.
  • A convergence towards quorum sensing deficiency was noted, correlating with decreased pyocyanin and protease production, reduced serum survival, and diminished twitching motility and cytotoxicity. Enhanced twitching was observed in one patient due to pilM and pilE changes.

Conclusions:

  • Emergence of antibiotic resistance in P. aeruginosa during VAP is associated with modifications in virulence.
  • Short-term pathoadaptation involving both resistance and virulence changes occurs during acute infections.
  • Further research is needed to explore the clinical consequences of these rapid adaptive changes.

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