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A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani
Leishmania parasites must survive and proliferate in two vastly different environments – the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. The change of temperature during the transmission from sandflies to mammals is both a key trigger for the progressio...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215717/ https://www.ncbi.nlm.nih.gov/pubmed/25179594 http://dx.doi.org/10.1242/jcs.157297 |
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author | Hombach, Antje Ommen, Gabi MacDonald, Andrea Clos, Joachim |
author_facet | Hombach, Antje Ommen, Gabi MacDonald, Andrea Clos, Joachim |
author_sort | Hombach, Antje |
collection | PubMed |
description | Leishmania parasites must survive and proliferate in two vastly different environments – the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. The change of temperature during the transmission from sandflies to mammals is both a key trigger for the progression of their life cycle and for elevated synthesis of heat shock proteins, which have been implicated in their survival at higher temperatures. Although the functions of the main heat shock protein families in the Leishmania life cycle have been studied, nothing is known about the roles played by small heat shock proteins. Here, we present the first evidence for the pivotal role played by the Leishmania donovani 23-kDa heat shock protein (which we called HSP23), which is expressed preferentially during the mammalian stage where it assumes a perinuclear localisation. Loss of HSP23 causes increased sensitivity to chemical stressors and renders L. donovani non-viable at 37°C. Consequently, HSP23-null mutants are non-infectious to primary macrophages in vitro. All phenotypic effects could be abrogated by the introduction of a functional HSP23 transgene into the null mutant, confirming the specificity of the mutant phenotype. Thus, HSP23 expression is a prerequisite for L. donovani survival at mammalian host temperatures and a crucial virulence factor. |
format | Online Article Text |
id | pubmed-4215717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Company of Biologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-42157172014-11-17 A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani Hombach, Antje Ommen, Gabi MacDonald, Andrea Clos, Joachim J Cell Sci Research Article Leishmania parasites must survive and proliferate in two vastly different environments – the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. The change of temperature during the transmission from sandflies to mammals is both a key trigger for the progression of their life cycle and for elevated synthesis of heat shock proteins, which have been implicated in their survival at higher temperatures. Although the functions of the main heat shock protein families in the Leishmania life cycle have been studied, nothing is known about the roles played by small heat shock proteins. Here, we present the first evidence for the pivotal role played by the Leishmania donovani 23-kDa heat shock protein (which we called HSP23), which is expressed preferentially during the mammalian stage where it assumes a perinuclear localisation. Loss of HSP23 causes increased sensitivity to chemical stressors and renders L. donovani non-viable at 37°C. Consequently, HSP23-null mutants are non-infectious to primary macrophages in vitro. All phenotypic effects could be abrogated by the introduction of a functional HSP23 transgene into the null mutant, confirming the specificity of the mutant phenotype. Thus, HSP23 expression is a prerequisite for L. donovani survival at mammalian host temperatures and a crucial virulence factor. The Company of Biologists 2014-11-01 /pmc/articles/PMC4215717/ /pubmed/25179594 http://dx.doi.org/10.1242/jcs.157297 Text en © 2014. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Hombach, Antje Ommen, Gabi MacDonald, Andrea Clos, Joachim A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani |
title | A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani |
title_full | A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani |
title_fullStr | A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani |
title_full_unstemmed | A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani |
title_short | A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani |
title_sort | small heat shock protein is essential for thermotolerance and intracellular survival of leishmania donovani |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215717/ https://www.ncbi.nlm.nih.gov/pubmed/25179594 http://dx.doi.org/10.1242/jcs.157297 |
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