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Article

Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity

1
Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil
2
Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre CEP 91501-970, RS, Brazil
3
Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Cellular and Molecular Biology, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil
4
Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil
5
Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS) and School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil
*
Author to whom correspondence should be addressed.
These authors have contributed equally to the work.
Present address: IRCCS-Istitutto Ortopedico Rizzoli, SSD Chemioterapia, via Pupilli 1, 40136 Bologna, Italy.
Academic Editor: Guido R.M.M. Haenen
Int. J. Mol. Sci. 2021, 22(13), 7205; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137205
Received: 11 June 2021 / Revised: 25 June 2021 / Accepted: 29 June 2021 / Published: 4 July 2021
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. View Full-Text
Keywords: Proteus mirabilis; urease; virulence factors; pathogenesis Proteus mirabilis; urease; virulence factors; pathogenesis
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MDPI and ACS Style

Grahl, M.V.C.; Uberti, A.F.; Broll, V.; Bacaicoa-Caruso, P.; Meirelles, E.F.; Carlini, C.R. Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity. Int. J. Mol. Sci. 2021, 22, 7205. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137205

AMA Style

Grahl MVC, Uberti AF, Broll V, Bacaicoa-Caruso P, Meirelles EF, Carlini CR. Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity. International Journal of Molecular Sciences. 2021; 22(13):7205. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137205

Chicago/Turabian Style

Grahl, Matheus V.C., Augusto F. Uberti, Valquiria Broll, Paula Bacaicoa-Caruso, Evelin F. Meirelles, and Celia R. Carlini 2021. "Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity" International Journal of Molecular Sciences 22, no. 13: 7205. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137205

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