Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis

Abstract 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...

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Autores principales:	Jakub Pawełczyk, Anna Brzostek, Alina Minias, Przemysław Płociński, Anna Rumijowska-Galewicz, Dominik Strapagiel, Jolanta Zakrzewska-Czerwińska, Jarosław Dziadek
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2aaf6f03abd245e3b8c2e78d904cd3c0
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spelling	oai:doaj.org-article:2aaf6f03abd245e3b8c2e78d904cd3c02021-12-02T17:30:53ZCholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis10.1038/s41598-021-91812-02045-2322https://doaj.org/article/2aaf6f03abd245e3b8c2e78d904cd3c02021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91812-0https://doaj.org/toc/2045-2322Abstract 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 B12 on Mtb transcriptome and the novel function of cobalamin in cholesterol metabolite dissipation which explains the probable role of B12 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.Jakub PawełczykAnna BrzostekAlina MiniasPrzemysław PłocińskiAnna Rumijowska-GalewiczDominik StrapagielJolanta Zakrzewska-CzerwińskaJarosław DziadekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jakub Pawełczyk Anna Brzostek Alina Minias Przemysław Płociński Anna Rumijowska-Galewicz Dominik Strapagiel Jolanta Zakrzewska-Czerwińska Jarosław Dziadek Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis
description	Abstract 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 B12 on Mtb transcriptome and the novel function of cobalamin in cholesterol metabolite dissipation which explains the probable role of B12 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	article
author	Jakub Pawełczyk Anna Brzostek Alina Minias Przemysław Płociński Anna Rumijowska-Galewicz Dominik Strapagiel Jolanta Zakrzewska-Czerwińska Jarosław Dziadek
author_facet	Jakub Pawełczyk Anna Brzostek Alina Minias Przemysław Płociński Anna Rumijowska-Galewicz Dominik Strapagiel Jolanta Zakrzewska-Czerwińska Jarosław Dziadek
author_sort	Jakub Pawełczyk
title	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_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_sort	cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to mycobacterium tuberculosis pathogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2aaf6f03abd245e3b8c2e78d904cd3c0
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Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis

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