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Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis
Mycobacterium tuberculosis (Mtb) is an obligate human pathogen that can adapt to the various nutrients available during its life cycle. However, in the nutritionally stringent environment of the macrophage phagolysosome, Mtb relies mainly on cholesterol. In previous studies, we demonstrated that Mtb...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196197/ https://www.ncbi.nlm.nih.gov/pubmed/34117327 http://dx.doi.org/10.1038/s41598-021-91812-0 |
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author | Pawełczyk, Jakub Brzostek, Anna Minias, Alina Płociński, Przemysław Rumijowska-Galewicz, Anna Strapagiel, Dominik Zakrzewska-Czerwińska, Jolanta Dziadek, Jarosław |
author_facet | Pawełczyk, Jakub Brzostek, Anna Minias, Alina Płociński, Przemysław Rumijowska-Galewicz, Anna Strapagiel, Dominik Zakrzewska-Czerwińska, Jolanta Dziadek, Jarosław |
author_sort | Pawełczyk, Jakub |
collection | PubMed |
description | Mycobacterium tuberculosis (Mtb) is an obligate human pathogen that can adapt to the various nutrients available during its life cycle. However, in the nutritionally stringent environment of the macrophage phagolysosome, Mtb relies mainly on cholesterol. In previous studies, we demonstrated that Mtb can accumulate and utilize cholesterol as the sole carbon source. However, a growing body of evidence suggests that a lipid-rich environment may have a much broader impact on the pathogenesis of Mtb infection than previously thought. Therefore, we applied high-resolution transcriptome profiling and the construction of various mutants to explore in detail the global effect of cholesterol on the tubercle bacillus metabolism. The results allow re-establishing the complete list of genes potentially involved in cholesterol breakdown. Moreover, we identified the modulatory effect of vitamin B(12) on Mtb transcriptome and the novel function of cobalamin in cholesterol metabolite dissipation which explains the probable role of B(12) in Mtb virulence. Finally, we demonstrate that a key role of cholesterol in mycobacterial metabolism is not only providing carbon and energy but involves also a transcriptome remodeling program that helps in developing tolerance to the unfavorable host cell environment far before specific stress-inducing phagosomal signals occur. |
format | Online Article Text |
id | pubmed-8196197 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81961972021-06-15 Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis Pawełczyk, Jakub Brzostek, Anna Minias, Alina Płociński, Przemysław Rumijowska-Galewicz, Anna Strapagiel, Dominik Zakrzewska-Czerwińska, Jolanta Dziadek, Jarosław Sci Rep Article Mycobacterium tuberculosis (Mtb) is an obligate human pathogen that can adapt to the various nutrients available during its life cycle. However, in the nutritionally stringent environment of the macrophage phagolysosome, Mtb relies mainly on cholesterol. In previous studies, we demonstrated that Mtb can accumulate and utilize cholesterol as the sole carbon source. However, a growing body of evidence suggests that a lipid-rich environment may have a much broader impact on the pathogenesis of Mtb infection than previously thought. Therefore, we applied high-resolution transcriptome profiling and the construction of various mutants to explore in detail the global effect of cholesterol on the tubercle bacillus metabolism. The results allow re-establishing the complete list of genes potentially involved in cholesterol breakdown. Moreover, we identified the modulatory effect of vitamin B(12) on Mtb transcriptome and the novel function of cobalamin in cholesterol metabolite dissipation which explains the probable role of B(12) in Mtb virulence. Finally, we demonstrate that a key role of cholesterol in mycobacterial metabolism is not only providing carbon and energy but involves also a transcriptome remodeling program that helps in developing tolerance to the unfavorable host cell environment far before specific stress-inducing phagosomal signals occur. Nature Publishing Group UK 2021-06-11 /pmc/articles/PMC8196197/ /pubmed/34117327 http://dx.doi.org/10.1038/s41598-021-91812-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Pawełczyk, Jakub Brzostek, Anna Minias, Alina Płociński, Przemysław Rumijowska-Galewicz, Anna Strapagiel, Dominik Zakrzewska-Czerwińska, Jolanta Dziadek, Jarosław Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis |
title | Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis |
title_full | Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis |
title_fullStr | Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis |
title_full_unstemmed | Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis |
title_short | Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis |
title_sort | cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to mycobacterium tuberculosis pathogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196197/ https://www.ncbi.nlm.nih.gov/pubmed/34117327 http://dx.doi.org/10.1038/s41598-021-91812-0 |
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