Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPase
Inada and Ido identified <i>Leptospira</i> sp. as the pathogen responsible for Weil’s Disease in 1915. Later, it was confirmed that Leptospira causes leptospirosis. The host microorganism’s interaction at the cellular level remained misunderstood for many years. Although different bacter...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/11/7/1695 |
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| author | Cassiano Felippe Gonçalves-de-Albuquerque Carolina Medina Coeli da Cunha Léo Victor Grimaldi de Castro Caroline de Azevedo Martins Marcos Roberto Colombo Barnese Patrícia Burth Mauricio Younes-Ibrahim |
| author_facet | Cassiano Felippe Gonçalves-de-Albuquerque Carolina Medina Coeli da Cunha Léo Victor Grimaldi de Castro Caroline de Azevedo Martins Marcos Roberto Colombo Barnese Patrícia Burth Mauricio Younes-Ibrahim |
| author_sort | Cassiano Felippe Gonçalves-de-Albuquerque |
| collection | DOAJ |
| description | Inada and Ido identified <i>Leptospira</i> sp. as the pathogen responsible for Weil’s Disease in 1915. Later, it was confirmed that Leptospira causes leptospirosis. The host microorganism’s interaction at the cellular level remained misunderstood for many years. Although different bacterial components have been isolated and purified, the complexity of the molecular interactions between these components and the host and the molecular mechanisms responsible for the systemic dysfunctions still needs to be fully unveiled. Leptospirosis affects virtually all animal species. Its cellular pathophysiology must involve a ubiquitous cellular mechanism in all eukaryotes. Na/K-ATPase is the molecular target of the leptospiral endotoxin (glycolipoprotein—GLP). Na/K-ATPase dysfunctions on different types of cells give rise to the organ disorders manifested in leptospirosis. Concomitantly, the development of a peculiar metabolic disorder characterized by dyslipidemia, with increased levels of circulating free fatty acids and an imbalance in the fatty acid/albumin molar ratio, triggers events of cellular lipotoxicity. Synergistically, multiple molecular stimuli are prompted during the infection, activating inflammasomes and Na/K-ATPase signalosome, leading to pro-inflammatory and metabolic alterations during leptospirosis. Leptospirosis involves diverse molecular mechanisms and alteration in patient inflammatory and metabolic status. Nonetheless, Na/K-ATPase is critical in the disease, and it is targeted by GLP, its components, and other molecules, such as fatty acids, that inhibit or trigger intracellular signaling through this enzyme. Herein, we overview the role of Na/K-ATPase during leptospirosis infection as a potential therapeutic target or an indicator of disease severity. |
| first_indexed | 2024-03-11T00:49:10Z |
| format | Article |
| id | doaj.art-b871fc7d216741efa1ae1286d33b57f4 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-11T00:49:10Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-b871fc7d216741efa1ae1286d33b57f42023-11-18T20:35:09ZengMDPI AGMicroorganisms2076-26072023-06-01117169510.3390/microorganisms11071695Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPaseCassiano Felippe Gonçalves-de-Albuquerque0Carolina Medina Coeli da Cunha1Léo Victor Grimaldi de Castro2Caroline de Azevedo Martins3Marcos Roberto Colombo Barnese4Patrícia Burth5Mauricio Younes-Ibrahim6Laboratory of Immunopharmacology, Department of Physiology, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20211-030, BrazilLaboratory of Immunopharmacology, Department of Physiology, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20211-030, BrazilCellular and Molecular Biology, Oswaldo Cruz Institute (IOC), Rio de Janeiro 21040-900, BrazilSchool of Medicine and Surgery, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20270-901, BrazilFISCLINEX Postgraduate Program, State University of Rio de Janeiro (UERJ), Rio de Janeiro 20550-900, BrazilLaboratory of Enzymology and Cellular Signaling, Department of Cellular and Molecular Biology, Federal Fluminense University (UFF), Niteroi 24000-000, BrazilFISCLINEX Postgraduate Program, State University of Rio de Janeiro (UERJ), Rio de Janeiro 20550-900, BrazilInada and Ido identified <i>Leptospira</i> sp. as the pathogen responsible for Weil’s Disease in 1915. Later, it was confirmed that Leptospira causes leptospirosis. The host microorganism’s interaction at the cellular level remained misunderstood for many years. Although different bacterial components have been isolated and purified, the complexity of the molecular interactions between these components and the host and the molecular mechanisms responsible for the systemic dysfunctions still needs to be fully unveiled. Leptospirosis affects virtually all animal species. Its cellular pathophysiology must involve a ubiquitous cellular mechanism in all eukaryotes. Na/K-ATPase is the molecular target of the leptospiral endotoxin (glycolipoprotein—GLP). Na/K-ATPase dysfunctions on different types of cells give rise to the organ disorders manifested in leptospirosis. Concomitantly, the development of a peculiar metabolic disorder characterized by dyslipidemia, with increased levels of circulating free fatty acids and an imbalance in the fatty acid/albumin molar ratio, triggers events of cellular lipotoxicity. Synergistically, multiple molecular stimuli are prompted during the infection, activating inflammasomes and Na/K-ATPase signalosome, leading to pro-inflammatory and metabolic alterations during leptospirosis. Leptospirosis involves diverse molecular mechanisms and alteration in patient inflammatory and metabolic status. Nonetheless, Na/K-ATPase is critical in the disease, and it is targeted by GLP, its components, and other molecules, such as fatty acids, that inhibit or trigger intracellular signaling through this enzyme. Herein, we overview the role of Na/K-ATPase during leptospirosis infection as a potential therapeutic target or an indicator of disease severity.https://www.mdpi.com/2076-2607/11/7/1695leptospirosisNa/K-ATPaseglycolipoproteinGLP |
| spellingShingle | Cassiano Felippe Gonçalves-de-Albuquerque Carolina Medina Coeli da Cunha Léo Victor Grimaldi de Castro Caroline de Azevedo Martins Marcos Roberto Colombo Barnese Patrícia Burth Mauricio Younes-Ibrahim Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPase Microorganisms leptospirosis Na/K-ATPase glycolipoprotein GLP |
| title | Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPase |
| title_full | Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPase |
| title_fullStr | Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPase |
| title_full_unstemmed | Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPase |
| title_short | Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPase |
| title_sort | cellular pathophysiology of leptospirosis role of na k atpase |
| topic | leptospirosis Na/K-ATPase glycolipoprotein GLP |
| url | https://www.mdpi.com/2076-2607/11/7/1695 |
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