The Role of Pseudomonas aeruginosa ExoY in an Acute Mouse Lung Infection Model
| Autor: | Justin Rothschuh, Bastian Schirmer, Tane Stelzer, Christina Kloth, Antje Munder, Roland Seifert |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis lcsh:Medicine Biology Toxicology medicine.disease_cause Article Type three secretion system Microbiology 03 medical and health sciences 0302 clinical medicine Bacterial Proteins medicine Animals Pseudomonas Infections bacterial effector protein Lung Respiratory Tract Infections nucleotidyl cyclase lung infection Pseudomonas aeruginosa Effector lcsh:R Bacterial effector protein T3SS Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Glucosyltransferases Cytokines Female Cytokine secretion Nucleotides Cyclic Uridine Monophosphate Bronchoalveolar Lavage Fluid 030217 neurology & neurosurgery Exotoxin Intracellular |
| Zdroj: | Toxins, Vol 10, Iss 5, p 185 (2018) Toxins; Volume 10; Issue 5; Pages: 185 Toxins |
| ISSN: | 2072-6651 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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