Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism

ABSTRACT Cholesterol of the host macrophage membrane is vital for mycobacterial infection, replication, and persistence. During chronic infection within host lung tissues, cholesterol facilitates the phagocytosis of mycobacteria into macrophages. Cholesterol degradation leads to increased ﬂux of ace...

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Autores principales:	Jun-Yu Xu, Lei Zhao, Ying Xu, Bolin Li, Linhui Zhai, Minjia Tan, Bang-Ce Ye
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	quantitative acetylome quantitative propionylome quantitative phosphorylome quantitative proteome cholesterol catabolism mycobacteria Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ef47479f589747a09e74baae315fb066
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spelling	oai:doaj.org-article:ef47479f589747a09e74baae315fb0662021-12-02T18:44:39ZDynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism10.1128/mSystems.00424-192379-5077https://doaj.org/article/ef47479f589747a09e74baae315fb0662020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00424-19https://doaj.org/toc/2379-5077ABSTRACT Cholesterol of the host macrophage membrane is vital for mycobacterial infection, replication, and persistence. During chronic infection within host lung tissues, cholesterol facilitates the phagocytosis of mycobacteria into macrophages. Cholesterol degradation leads to increased ﬂux of acetyl-coenzyme A (CoA) and propionyl-CoA, providing energy and building blocks for virulence macromolecules as well as donors for global protein acylation. Potential functions of lysine acylation are gradually revealed in bacterial survival and pathogenesis. However, the mycobacterial proteome and posttranslational modification (PTM) changes involved in the cholesterol catabolism bioprocess remain unclear. Here, we used nonpathogenic Mycobacterium smegmatis as a model and simultaneously monitored mycobacterial proteome and acetylome changes in the presence of glucose and cholesterol. We discovered that cholesterol metabolic enzymes were upregulated with respect to both protein expression levels and lysine acylation levels during the metabolic shift from glucose to cholesterol. After that, adenylating enzymes related to cholesterol metabolism were proven to be precisely regulated at the propionylation level by mycobacterial acyltransferase M. smegmatis Kat (MsKat) in response to cellular propionyl-CoA accumulation. Furthermore, the kinase expression and phosphorylation levels were also changed along with fluctuations in cholesterol levels. Our results expanded current knowledge of acylation regulation in the cholesterol catabolism of mycobacteria and provided references for possible antimycobacterium strategy. IMPORTANCE Cholesterol assimilation is a critical step in mycobacterial chronic infection. However, knowledge from the dynamic characterization of cholesterol metabolism in mycobacteria at the protein expression and PTM levels remains limited. Our study uncovered the landscape of protein expression, lysine acetylation, lysine propionylation, and S/T/Y phosphorylation during the metabolic changes from glucose to cholesterol in mycobacteria. The data showed that cholesterol-induced carbon shift resulted in the elevation of protein expression and lysine acylation in diverse metabolic enzymes involved in cholesterol degradation and that the presence of cholesterol also promoted the perturbations at the phosphorylation level in the kinase system in mycobacteria. This study systematically characterized the regulation of cholesterol catabolism at several different levels, which provided the detailed references in mycobacterial proteome and potential antimycobacterial strategies.Jun-Yu XuLei ZhaoYing XuBolin LiLinhui ZhaiMinjia TanBang-Ce YeAmerican Society for Microbiologyarticlequantitative acetylomequantitative propionylomequantitative phosphorylomequantitative proteomecholesterol catabolismmycobacteriaMicrobiologyQR1-502ENmSystems, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	quantitative acetylome quantitative propionylome quantitative phosphorylome quantitative proteome cholesterol catabolism mycobacteria Microbiology QR1-502
spellingShingle	quantitative acetylome quantitative propionylome quantitative phosphorylome quantitative proteome cholesterol catabolism mycobacteria Microbiology QR1-502 Jun-Yu Xu Lei Zhao Ying Xu Bolin Li Linhui Zhai Minjia Tan Bang-Ce Ye Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism
description	ABSTRACT Cholesterol of the host macrophage membrane is vital for mycobacterial infection, replication, and persistence. During chronic infection within host lung tissues, cholesterol facilitates the phagocytosis of mycobacteria into macrophages. Cholesterol degradation leads to increased ﬂux of acetyl-coenzyme A (CoA) and propionyl-CoA, providing energy and building blocks for virulence macromolecules as well as donors for global protein acylation. Potential functions of lysine acylation are gradually revealed in bacterial survival and pathogenesis. However, the mycobacterial proteome and posttranslational modification (PTM) changes involved in the cholesterol catabolism bioprocess remain unclear. Here, we used nonpathogenic Mycobacterium smegmatis as a model and simultaneously monitored mycobacterial proteome and acetylome changes in the presence of glucose and cholesterol. We discovered that cholesterol metabolic enzymes were upregulated with respect to both protein expression levels and lysine acylation levels during the metabolic shift from glucose to cholesterol. After that, adenylating enzymes related to cholesterol metabolism were proven to be precisely regulated at the propionylation level by mycobacterial acyltransferase M. smegmatis Kat (MsKat) in response to cellular propionyl-CoA accumulation. Furthermore, the kinase expression and phosphorylation levels were also changed along with fluctuations in cholesterol levels. Our results expanded current knowledge of acylation regulation in the cholesterol catabolism of mycobacteria and provided references for possible antimycobacterium strategy. IMPORTANCE Cholesterol assimilation is a critical step in mycobacterial chronic infection. However, knowledge from the dynamic characterization of cholesterol metabolism in mycobacteria at the protein expression and PTM levels remains limited. Our study uncovered the landscape of protein expression, lysine acetylation, lysine propionylation, and S/T/Y phosphorylation during the metabolic changes from glucose to cholesterol in mycobacteria. The data showed that cholesterol-induced carbon shift resulted in the elevation of protein expression and lysine acylation in diverse metabolic enzymes involved in cholesterol degradation and that the presence of cholesterol also promoted the perturbations at the phosphorylation level in the kinase system in mycobacteria. This study systematically characterized the regulation of cholesterol catabolism at several different levels, which provided the detailed references in mycobacterial proteome and potential antimycobacterial strategies.
format	article
author	Jun-Yu Xu Lei Zhao Ying Xu Bolin Li Linhui Zhai Minjia Tan Bang-Ce Ye
author_facet	Jun-Yu Xu Lei Zhao Ying Xu Bolin Li Linhui Zhai Minjia Tan Bang-Ce Ye
author_sort	Jun-Yu Xu
title	Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism
title_short	Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism
title_full	Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism
title_fullStr	Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism
title_full_unstemmed	Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism
title_sort	dynamic characterization of protein and posttranslational modification levels in mycobacterial cholesterol catabolism
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/ef47479f589747a09e74baae315fb066
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_version_	1718377714735382528

Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism

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