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dc.contributor.authorScheithauer, Lina
dc.contributor.authorThiem, Stefanie
dc.contributor.authorSchmelz, Stefan
dc.contributor.authorDellmann, Ansgar
dc.contributor.authorBuessow, Konrad
dc.contributor.authorBrouwer, Rene M. H. J.
dc.contributor.authorÜnal, Can Murat
dc.contributor.authorBlankenfeldt, Wulf
dc.contributor.authorSteinert, Michael
dc.date.accessioned2021-03-08T09:48:19Z
dc.date.available2021-03-08T09:48:19Z
dc.date.issued2021en_US
dc.identifier.citationScheithauer, L., Thiem, S., Schmelz, S., Dellmann, A., Büssow, K., Brouwer, R. M., ... & Steinert, M. (2021). Zinc metalloprotease ProA of Legionella pneumophila increases alveolar septal thickness in human lung tissue explants by collagen IV degradation. Cellular Microbiology, e13313.en_US
dc.identifier.issn1462-5814
dc.identifier.issn1462-5822
dc.identifier.urihttps://hdl.handle.net/20.500.12846/528
dc.description.abstractProA is a secreted zinc metalloprotease of Legionella pneumophila causing lung damage in animal models of Legionnaires' disease. Here we demonstrate that ProA promotes infection of human lung tissue explants (HLTEs) and dissect the contribution to cell type specific replication and extracellular virulence mechanisms. For the first time, we reveal that co-incubation of HLTEs with purified ProA causes a significant increase of the alveolar septal thickness. This destruction of connective tissue fibres was further substantiated by collagen IV degradation assays. The moderate attenuation of a proA-negative mutant in A549 epithelial cells and THP-1 macrophages suggests that effects of ProA in tissue mainly result from extracellular activity. Correspondingly, ProA contributes to dissemination and serum resistance of the pathogen, which further expands the versatile substrate spectrum of this thermolysin-like protease. The crystal structure of ProA at 1.48 Å resolution showed high congruence to pseudolysin of Pseudomonas aeruginosa, but revealed deviations in flexible loops, the substrate binding pocket S1 ' and the repertoire of cofactors, by which ProA can be distinguished from respective homologues. In sum, this work specified virulence features of ProA at different organisational levels by zooming in from histopathological effects in human lung tissue to atomic details of the protease substrate determination.en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.isversionof10.1111/cmi.13313en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectLegionella Pneumophilaen_US
dc.subjectZinc Metalloproteaseen_US
dc.subjectKristal Yapıen_US
dc.subjectCrystal Structureen_US
dc.titleZinc metalloprotease ProA of Legionella pneumophila increases alveolar septal thickness in human lung tissue explants by collagen IV degradationen_US
dc.typearticleen_US
dc.relation.journalCellular Microbiologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.contributor.departmentTAÜ, Fen Fakültesi, Moleküler Biyoteknoloji Bölümüen_US
dc.contributor.institutionauthorÜnal, Can Murat


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