Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity
Autor: | Augusto F. Uberti, Matheus V. Coste Grahl, Paula Bacaicoa-Caruso, Evelin F Meirelles, Célia R. Carlini, Valquiria Broll |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cell type Urease QH301-705.5 virulence factors Virulence Catalysis Article Microbiology Inorganic Chemistry 03 medical and health sciences 0302 clinical medicine medicine Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Pathogen Proteus mirabilis Spectroscopy chemistry.chemical_classification urease Reactive oxygen species biology Microglia Chemistry pathogenesis Organic Chemistry General Medicine biology.organism_classification Computer Science Applications 030104 developmental biology medicine.anatomical_structure biology.protein 030217 neurology & neurosurgery Intracellular |
Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 13 International Journal of Molecular Sciences, Vol 22, Iss 7205, p 7205 (2021) |
ISSN: | 1422-0067 |
Popis: | Infection by Proteus mirabilis causes urinary stones and catheter incrustation due to ammonia formed by urease (PMU), one of its virulence factors. Non-enzymatic properties, such as pro-inflammatory and neurotoxic activities, were previously reported for distinct ureases, including that of the gastric pathogen Helicobacter pylori. Here, PMU was assayed on isolated cells to evaluate its non-enzymatic properties. Purified PMU (nanomolar range) was tested in human (platelets, HEK293 and SH-SY5Y) cells, and in murine microglia (BV-2). PMU promoted platelet aggregation. It did not affect cellular viability and no ammonia was detected in the cultures’ supernatants. PMU-treated HEK293 cells acquired a pro-inflammatory phenotype, producing reactive oxygen species (ROS) and cytokines IL-1β and TNF-α. SH-SY5Y cells stimulated with PMU showed high levels of intracellular Ca2+ and ROS production, but unlike BV-2 cells, SH-SY5Y did not synthesize TNF-α and IL-1β. Texas Red-labeled PMU was found in the cytoplasm and in the nucleus of all cell types. Bioinformatic analysis revealed two bipartite nuclear localization sequences in PMU. We have shown that PMU, besides urinary stone formation, can potentially contribute in other ways to pathogenesis. Our data suggest that PMU triggers pro-inflammatory effects and may affect cells beyond the renal system, indicating a possible role in extra-urinary diseases. |
Databáze: | OpenAIRE |
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