Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis

Abstract Recent data indicate that the metabolism of Mycobacterium tuberculosis (Mtb) inside its host cell is heavily dependent on cholesterol and fatty acids. Mtb exhibits a unique capacity to co-metabolize different carbon sources and the products from these substrates are compartmentalized metabo...

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Autores principales:	Wonsik Lee, Brian C. VanderVen, Suzanne Walker, David G. Russell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f6c81e6275fa44bfb16513cf85230f7e
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spelling	oai:doaj.org-article:f6c81e6275fa44bfb16513cf85230f7e2021-12-02T15:06:02ZNovel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis10.1038/s41598-017-00067-12045-2322https://doaj.org/article/f6c81e6275fa44bfb16513cf85230f7e2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00067-1https://doaj.org/toc/2045-2322Abstract Recent data indicate that the metabolism of Mycobacterium tuberculosis (Mtb) inside its host cell is heavily dependent on cholesterol and fatty acids. Mtb exhibits a unique capacity to co-metabolize different carbon sources and the products from these substrates are compartmentalized metabolically. Isocitrate lies at one of the key nodes of carbon metabolism and can feed into either the glyoxylate shunt (via isocitrate lyase) or the TCA cycle (via isocitrate dehydrogenase (ICDH) activity) and we sought to better understand the regulation at this junction. An isocitrate lyase-deficient mutant of Mtb (Δicl1) exhibited a delayed growth phenotype in stearic acid (C18 fatty acid) media and we isolated rescue mutants that had lost this growth delay. We found that mutations in the gene rv2170 promoted Mtb replication under these conditions and rescued the growth delay in a Δicl1 background. The Mtb Rv2170 protein shows lysine acetyltransferase activity, which is capable of post-translationally modifying lysine residues of the ICDH protein leading to a reduction in its enzymatic activity. Our data show that contrary to most bacteria that regulate ICDH activity through phosphorylation, Mtb is capable of regulating ICDH activity by acetylation. This mechanism of regulation is similar to that utilized for mammalian mitochondrial ICDH.Wonsik LeeBrian C. VanderVenSuzanne WalkerDavid G. RussellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wonsik Lee Brian C. VanderVen Suzanne Walker David G. Russell Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis
description	Abstract Recent data indicate that the metabolism of Mycobacterium tuberculosis (Mtb) inside its host cell is heavily dependent on cholesterol and fatty acids. Mtb exhibits a unique capacity to co-metabolize different carbon sources and the products from these substrates are compartmentalized metabolically. Isocitrate lies at one of the key nodes of carbon metabolism and can feed into either the glyoxylate shunt (via isocitrate lyase) or the TCA cycle (via isocitrate dehydrogenase (ICDH) activity) and we sought to better understand the regulation at this junction. An isocitrate lyase-deficient mutant of Mtb (Δicl1) exhibited a delayed growth phenotype in stearic acid (C18 fatty acid) media and we isolated rescue mutants that had lost this growth delay. We found that mutations in the gene rv2170 promoted Mtb replication under these conditions and rescued the growth delay in a Δicl1 background. The Mtb Rv2170 protein shows lysine acetyltransferase activity, which is capable of post-translationally modifying lysine residues of the ICDH protein leading to a reduction in its enzymatic activity. Our data show that contrary to most bacteria that regulate ICDH activity through phosphorylation, Mtb is capable of regulating ICDH activity by acetylation. This mechanism of regulation is similar to that utilized for mammalian mitochondrial ICDH.
format	article
author	Wonsik Lee Brian C. VanderVen Suzanne Walker David G. Russell
author_facet	Wonsik Lee Brian C. VanderVen Suzanne Walker David G. Russell
author_sort	Wonsik Lee
title	Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis
title_short	Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis
title_full	Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis
title_fullStr	Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis
title_full_unstemmed	Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis
title_sort	novel protein acetyltransferase, rv2170, modulates carbon and energy metabolism in mycobacterium tuberculosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f6c81e6275fa44bfb16513cf85230f7e
work_keys_str_mv	AT wonsiklee novelproteinacetyltransferaserv2170modulatescarbonandenergymetabolisminmycobacteriumtuberculosis AT briancvanderven novelproteinacetyltransferaserv2170modulatescarbonandenergymetabolisminmycobacteriumtuberculosis AT suzannewalker novelproteinacetyltransferaserv2170modulatescarbonandenergymetabolisminmycobacteriumtuberculosis AT davidgrussell novelproteinacetyltransferaserv2170modulatescarbonandenergymetabolisminmycobacteriumtuberculosis
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Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis

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