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Int J Biochem Cell Biol. 2015 Feb;59:193-202. doi: 10.1016/j.biocel.2014.11.010. Epub 2014 Nov 29.

Proteome-wide lysine acetylation profiling of the human pathogen Mycobacterium tuberculosis.

Author information

1
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.
2
National Clinical Laboratory on Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
3
National Clinical Laboratory on Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China. Electronic address: hairong.huangcn@gmail.com.
4
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.

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.

KEYWORDS:

Antibiotic resistance; Mycobacterium; N(ɛ)-lysine acetylation; Persistence; Virulence

PMID:
25456444
DOI:
10.1016/j.biocel.2014.11.010
[Indexed for MEDLINE]

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