The Pseudomonas aeruginosa ExoY phenotype of high-copy-number recombinants is not detectable in natural isolates

Author:

Munder Antje12ORCID,Rothschuh Justin3,Schirmer Bastian3ORCID,Klockgether Jens1,Kaever Volkhard4,Tümmler Burkhard12,Seifert Roland3,Kloth Christina35

Affiliation:

1. Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany

2. Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, Hannover, Germany

3. Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany

4. Research Core Unit Metabolomics, Hannover Medical School, 30625 Hannover, Germany

5. Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany

Abstract

The nucleotidyl cyclase ExoY is an effector protein of the type III secretion system of Pseudomonas aeruginosa . We compared the cyclic nucleotide production and lung disease phenotypes caused by the ExoY-overexpressing strain PA103Δ exoUexoT::Tc pUCP exoY , its vector control strain PA103Δ exoUexoT::Tc pUCP18, its loss-of-function control PA103Δ exoUexoT::Tc pUCP exoY K81M and natural ExoY-positive and ExoY-negative isolates in a murine acute airway infection model. Only the P. aeruginosa carrier of the exoY- plasmid produced high levels of cUMP and caused the most severe course of infection. The pathology ascribed to ExoY from studies using the high-copy-number plasmid on mammalian cells in vitro and in vivo was not observed with natural P. aeruginosa isolates. This indicates that the role of ExoY during infection with real-life P. aeruginosa still needs to be resolved.

Funder

Medizinischen Hochschule Hannover

Publisher

The Royal Society

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology,General Neuroscience

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