Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism
文献类型：期刊论文
| 作者 | Xu, Jun-Yu1,2; Zhao, Lei1; Xu, Ying1; Li, Bolin2; Zhai, Linhui2; Tan, Minjia2 ; Ye, Bang-Ce1
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| 刊名 | MSYSTEMS
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| 出版日期 | 2020 |
| 卷号 | 5期号:1页码:16 |
| ISSN号 | 2379-5077 |
| 关键词 | quantitative acetylome quantitative propionylome quantitative phosphorylome quantitative proteome cholesterol catabolism mycobacteria |
| DOI | 10.1128/mSystems.00424-19 |
| 通讯作者 | Tan, Minjia(mjtan@simm.ac.cn) ; Ye, Bang-Ce(bcye@ecust.edu.cn) |
| 英文摘要 | 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 acyl-transferase 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. |
| WOS关键词 | LYSINE SUCCINYLATION ; METHYLCITRATE CYCLE ; ANALYSIS REVEALS ; TUBERCULOSIS ; METABOLISM ; ACETYLATION ; KINASE ; IDENTIFICATION ; REQUIRES ; ACIDURIA |
| 资助项目 | National Key Research and Development Program of China[2018YFA0900404] ; National Natural Science Foundation of China[31730004] ; National Natural Science Foundation of China[21575089] ; Natural Science Foundation of China[31670066] ; Natural Science Foundation of China[91753203] ; Natural Science Foundation of China[91853126] ; China Postdoctoral Science Foundation[2019T120368] ; Shanghai Sailing Program[19YF1457700] ; 2018 SA-SIBS Scholarship Program |
| WOS研究方向 | Microbiology |
| 语种 | 英语 |
| 出版者 | AMER SOC MICROBIOLOGY |
| WOS记录号 | WOS:000518855000048 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/281168]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Tan, Minjia; Ye, Bang-Ce |
| 作者单位 | 1.East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Jun-Yu,Zhao, Lei,Xu, Ying,et al. Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism[J]. MSYSTEMS,2020,5(1):16. |
| APA | Xu, Jun-Yu.,Zhao, Lei.,Xu, Ying.,Li, Bolin.,Zhai, Linhui.,...&Ye, Bang-Ce.(2020).Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism.MSYSTEMS,5(1),16. |
| MLA | Xu, Jun-Yu,et al."Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism".MSYSTEMS 5.1(2020):16. |
入库方式： OAI收割
来源：上海药物研究所
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