title: Proteome-wide lysine acetylation profiling of the human pathogen Mycobacterium tuberculosis.
abstract: N(ɛ)-Acetylation of lysine residues represents a pivotal post-translational modification used by both eukaryotes and prokaryotes to modulate diverse biological processes. Mycobacterium tuberculosis is the causative agent of tuberculosis, one of the most formidable public health threats. Many aspects of the biology of M. tuberculosis remain elusive, in particular the extent and function of N(ɛ)-lysine acetylation. With a combination of anti-acetyllysine antibody-based immunoaffinity enrichment with high-resolution mass spectrometry, we identified 1128 acetylation sites on 658 acetylated M. tuberculosis proteins. GO analysis of the acetylome showed that acetylated proteins are involved in the regulation of diverse cellular processes including metabolism and protein synthesis. Six types of acetylated peptide sequence motif were revealed from the acetylome. Twenty lysine-acetylated proteins showed homology with acetylated proteins previously identified from Escherichia coli, Salmonella enterica, Bacillus subtilis and Streptomyces roseosporus, with several acetylation sites highly conserved among four or five bacteria, suggesting that acetylated proteins are more conserved. Notably, several proteins including isocitrate lyase involved in the persistence, virulence and antibiotic resistance are acetylated, and site-directed mutagenesis of isocitrate lyase acetylation site to glutamine led to a decrease of the enzyme activity, indicating major roles of KAc in these proteins engaged cellular processes. Our data firstly provides a global survey of M. tuberculosis acetylation, and implicates extensive regulatory role of acetylation in this pathogen. This may serve as an important basis to address the roles of lysine acetylation in M. tuberculosis metabolism, persistence and virulence.
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Longxiang
authors.initials: L
authors.lastname: Xie
authors.affiliation: National Clinical Laboratory on Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Xiangke
authors.initials: X
authors.lastname: Duan
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Luo
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Pang
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Guojian
authors.initials: G
authors.lastname: Liao
authors.affiliation: National Clinical Laboratory on Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yu
authors.affiliation: National Clinical Laboratory on Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
authors.forename: Yunxu
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Clinical Laboratory on Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China. Electronic address: hairong.huangcn@gmail.com.
authors.forename: Hairong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China. Electronic address: jianpingxiefudan@gmail.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
mesh_terms: D000107:Acetylation; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D017124:Conserved Sequence; D004352:Drug Resistance, Microbial; D019143:Evolution, Molecular; D063990:Gene Ontology; D006801:Humans; D007522:Isocitrate Lyase / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009169:Mycobacterium tuberculosis / Q000378:metabolism* / Q000472:pathogenicity; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D010455:Peptides; D020543:Proteome; D007522:Isocitrate Lyase; D008239:Lysine
keywords: Antibiotic resistance; Mycobacterium; N(ɛ)-lysine acetylation; Persistence; Virulence