Nε- and O‑Acetylation in Mycobacterium tuberculosis Lineage 7 and Lineage 4 Strains: Proteins Involved in Bioenergetics, Virulence, and Antimicrobial Resistance Are Acetylated

• Published in: Journal of proteome research 2017-11, Vol.16 (11), p.4045-4059
• Main Authors: Birhanu, Alemayehu Godana, Yimer, Solomon Abebe, Holm-Hansen, Carol, Norheim, Gunnstein, Aseffa, Abraham, Abebe, Markos, Tønjum, Tone
• Format: Article
• Language: English
• Subjects: Acetylation; Anti-Bacterial Agents; Bacterial Proteins - metabolism; Energy Metabolism; Gene Expression Regulation, Bacterial; Mycobacterium tuberculosis - chemistry; Mycobacterium tuberculosis - metabolism; Protein Processing, Post-Translational; Species Specificity; Virulence
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/acs.jproteome.7b00429

Increasing evidence demonstrates that lysine acetylation is involved in Mycobacterium tuberculosis (Mtb) virulence and pathogenesis. However, previous investigations in Mtb have only monitored acetylation at lysine residues using selected reference strains. We analyzed the global Nε- and O-acetylation of three Mtb isolates: two lineage 7 clinical isolates and the lineage 4 H37Rv reference strain. Quantitative acetylome analysis resulted in identification of 2490 class-I acetylation sites, 2349 O-acetylation and 141 Nε-acetylation sites, derived from 953 unique proteins. Mtb O-acetylation was thereby significantly more abundant than Nε-acetylation. The acetylated proteins were found to be involved in central metabolism, translation, stress responses, and antimicrobial drug resistance. Notably, 261 acetylation sites on 165 proteins were differentially regulated between lineage 7 and lineage 4 strains. A total of 257 acetylation sites on 161 proteins were hypoacetylated in lineage 7 strains. These proteins are involved in Mtb growth, virulence, bioenergetics, host–pathogen interactions, and stress responses. This study provides the first global analysis of O-acetylated proteins in Mtb. This quantitative acetylome data expand the current understanding regarding the nature and diversity of acetylated proteins in Mtb and open a new avenue of research for exploring the role of protein acetylation in Mtb physiology.