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Toxins 2018, 10(5), 185; https://doi.org/10.3390/toxins10050185

The Role of Pseudomonas aeruginosa ExoY in an Acute Mouse Lung Infection Model

1
Institute of Pharmacology, Hannover Medical School, 30625 Hannover, Germany
2
Clinic for Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany
3
Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany
4
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research, 30625 Hannover, Germany
These authors contributed equally to this paper and are listed in alphabetical order of their surnames.
*
Author to whom correspondence should be addressed.
Received: 14 March 2018 / Revised: 20 April 2018 / Accepted: 2 May 2018 / Published: 4 May 2018
(This article belongs to the Section Bacterial Toxins)
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Abstract

The effector protein Exotoxin Y (ExoY) produced by Pseudomonas aeruginosa is injected via the type III secretion system (T3SS) into host cells. ExoY acts as nucleotidyl cyclase promoting the intracellular accumulation of cyclic nucleotides. To what extent nucleotidyl cyclase activity contributes to the pathogenicity of ExoY and which mechanisms participate in the manifestation of lung infection is still unclear. Here, we used an acute airway infection model in mice to address the role of ExoY in lung infection. In infected lungs, a dose-dependent phenotype of infection with bacteria-expressing ExoY was mirrored by haemorrhage, formation of interstitial oedema in alveolar septa, and infiltration of the perivascular space with erythrocytes and neutrophilic granulocytes. Analyses of the infection process on the cellular and organismal level comparing infections with Pseudomonas aeruginosa mutants expressing either nucleotidyl cyclase-active or -inactive ExoY revealed differential cytokine secretion, increased prevalence of apoptosis, and a break of lung barrier integrity in mice infected with cyclase-active ExoY. Notably, of all measured cyclic nucleotides, only the increase of cyclic UMP in infected mouse lungs coincides temporally with the observed early pathologic changes. In summary, our results suggest that the nucleotidyl cyclase activity of ExoY can contribute to P. aeruginosa acute pathogenicity. View Full-Text
Keywords: Pseudomonas aeruginosa; bacterial effector protein; nucleotidyl cyclase; lung infection; T3SS Pseudomonas aeruginosa; bacterial effector protein; nucleotidyl cyclase; lung infection; T3SS
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Kloth, C.; Schirmer, B.; Munder, A.; Stelzer, T.; Rothschuh, J.; Seifert, R. The Role of Pseudomonas aeruginosa ExoY in an Acute Mouse Lung Infection Model. Toxins 2018, 10, 185.

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