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

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 gastr...

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Autores principales: Grahl, Matheus V. C., Uberti, Augusto F., Broll, Valquiria, Bacaicoa-Caruso, Paula, Meirelles, Evelin F., Carlini, Celia R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268090/
https://www.ncbi.nlm.nih.gov/pubmed/34281258
http://dx.doi.org/10.3390/ijms22137205
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author Grahl, Matheus V. C.
Uberti, Augusto F.
Broll, Valquiria
Bacaicoa-Caruso, Paula
Meirelles, Evelin F.
Carlini, Celia R.
author_facet Grahl, Matheus V. C.
Uberti, Augusto F.
Broll, Valquiria
Bacaicoa-Caruso, Paula
Meirelles, Evelin F.
Carlini, Celia R.
author_sort Grahl, Matheus V. C.
collection PubMed
description 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 Ca(2+) 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.
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spelling pubmed-82680902021-07-10 Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity Grahl, Matheus V. C. Uberti, Augusto F. Broll, Valquiria Bacaicoa-Caruso, Paula Meirelles, Evelin F. Carlini, Celia R. Int J Mol Sci Article 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 Ca(2+) 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. MDPI 2021-07-04 /pmc/articles/PMC8268090/ /pubmed/34281258 http://dx.doi.org/10.3390/ijms22137205 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Grahl, Matheus V. C.
Uberti, Augusto F.
Broll, Valquiria
Bacaicoa-Caruso, Paula
Meirelles, Evelin F.
Carlini, Celia R.
Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity
title Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity
title_full Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity
title_fullStr Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity
title_full_unstemmed Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity
title_short Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity
title_sort proteus mirabilis urease: unsuspected non-enzymatic properties relevant to pathogenicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268090/
https://www.ncbi.nlm.nih.gov/pubmed/34281258
http://dx.doi.org/10.3390/ijms22137205
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