mSystems (Dec 2020)

Phenotypic and Genomic Comparison of the Two Most Common ExoU-Positive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Clones, PA14 and ST235

  • Sebastian Fischer,
  • Sarah Dethlefsen,
  • Jens Klockgether,
  • Burkhard Tümmler

DOI
https://doi.org/10.1128/mSystems.01007-20
Journal volume & issue
Vol. 5, no. 6

Abstract

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ABSTRACT Genotyping of 2,882 Pseudomonas aeruginosa isolates that had been collected during the last 40 years identified the ExoU-positive lineages PA14 (ST253) and ST235 as the second and third most frequent clones in the P. aeruginosa population. Both clones were approximately 2-fold more frequently detected in animate habitats than in soil or aquatic habitats. While ST253 clone isolates were causing mainly acute and chronic infections in humans, ST235 isolates had been preferentially collected from hospitalized patients with severe acute infections, particularly, keratitis, urinary tract infections, burn wounds, and ventilator-associated pneumonia. The two major exoU clones differed substantially in the composition and flexibility of the accessory genome and by more than 8,000 amino acid sequences. Pronounced sequence variation between orthologs was noted in genes encoding elements of secretion systems and secreted effector molecules, including the type III secretion system, indicating the modes of action of the different clones. When comparing representatives of the two clones in batch culture, the PA14 strain orchestrated the quorum sensing circuitry for the expression of pathogenic traits and stopped growing in batch culture when it entered the stationary phase, but the quorum sensing-deficient ST235 strain expressed high type III secretion activity and continued to grow and to divide. In summary, unrestricted growth, high constitutive type III secretion activity, and facilitated uptake of foreign DNA could be major features that have made ST235 a global high-risk clone associated with poor outcomes of acute nosocomial infections. IMPORTANCE The ubiquitous and metabolically versatile environmental bacterium Pseudomonas aeruginosa can cause infections in a wide variety of hosts, including insects, plants, animals, and humans. P. aeruginosa is one of the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens that are the major cause of nosocomial infections in the United States and are a threat all over the world because of their capacity to become increasingly resistant to all available antibiotics. Most experimental work on P. aeruginosa has been performed with reference strains PAO1 and PA14, providing deep insight into key metabolic and regulatory pathways thought to be applicable to all P. aeruginosa strains. However, this comparative study on the two most common exoU-positive clones taught us that there are major lineages in the population such as the global high-risk clone ST235 that exhibit uncommon traits of lifestyle, genome mobility, and pathogenicity distinct from those in our knowledge gained from the studies with the reference strains.

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