title: Acetylome analysis reveals diverse functions of lysine acetylation in Mycobacterium tuberculosis.
abstract: The lysine acetylation of proteins is a reversible post-translational modification that plays a critical regulatory role in both eukaryotes and prokaryotes. Mycobacterium tuberculosis is a facultative intracellular pathogen and the causative agent of tuberculosis. Increasing evidence shows that lysine acetylation may play an important role in the pathogenesis of M. tuberculosis. However, only a few acetylated proteins of M. tuberculosis are known, presenting a major obstacle to understanding the functional roles of reversible lysine acetylation in this pathogen. We performed a global acetylome analysis of M. tuberculosis H37Ra by combining protein/peptide prefractionation, antibody enrichment, and LC-MS/MS. In total, we identified 226 acetylation sites in 137 proteins of M. tuberculosis H37Ra. The identified acetylated proteins were functionally categorized into an interaction map and shown to be involved in various biological processes. Consistent with previous reports, a large proportion of the acetylation sites were present on proteins involved in glycolysis/gluconeogenesis, the citrate cycle, and fatty acid metabolism. A NAD(+)-dependent deacetylase (MRA_1161) deletion mutant of M. tuberculosis H37Ra was constructed and its characterization showed a different colony morphology, reduced biofilm formation, and increased tolerance of heat stress. Interestingly, lysine acetylation was found, for the first time, to block the immunogenicity of a peptide derived from a known immunogen, HspX, suggesting that lysine acetylation plays a regulatory role in immunogenicity. Our data provide the first global survey of lysine acetylation in M. tuberculosis. The dataset should be an important resource for the functional analysis of lysine acetylation in M. tuberculosis and facilitate the clarification of the entire metabolic networks of this life-threatening pathogen.
authors.affiliation: From the ‡Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
authors.forename: Fengying
authors.initials: F
authors.lastname: Liu
authors.affiliation: §Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
authors.forename: Mingkun
authors.initials: M
authors.lastname: Yang
authors.affiliation: From the ‡Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
authors.forename: Xude
authors.initials: X
authors.lastname: Wang
authors.affiliation: From the ‡Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yang
authors.affiliation: From the ‡Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
authors.forename: Jing
authors.initials: J
authors.lastname: Gu
authors.affiliation: ¶Foshan Fourth People's Hospital, Foshan, China;
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: ‖National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China gefeng@ihb.ac.cn dengjy@wh.iov.cn zhangxe@sun5.ibp.ac.cn.
authors.forename: Xian-En
authors.initials: XE
authors.lastname: Zhang
authors.affiliation: From the ‡Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; gefeng@ihb.ac.cn dengjy@wh.iov.cn zhangxe@sun5.ibp.ac.cn.
authors.forename: Jiaoyu
authors.initials: J
authors.lastname: Deng
authors.affiliation: §Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; gefeng@ihb.ac.cn dengjy@wh.iov.cn zhangxe@sun5.ibp.ac.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Ge
mesh_terms: D000107:Acetylation; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005943:Gluconeogenesis / Q000235:genetics; D006019:Glycolysis / Q000235:genetics; D056545:Group III Histone Deacetylases / Q000172:deficiency / Q000235:genetics; D008239:Lysine / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005227:Fatty Acids; D020543:Proteome; D056545:Group III Histone Deacetylases; D008239:Lysine