Proteome-wide Lysine Glutarylation Profiling of the <i>Mycobacterium tuberculosis</i> H37Rv

Lysine glutarylation, a new protein posttranslational modification (PTM), was recently identified and characterized in both prokaryotic and eukaryotic cells. To explore the distribution of lysine glutarylation in <i>Mycobacterium tuberculsosis</i>, by using a comprehensive method combining the immune affinity peptide enrichment by the glutaryl-lysine antibody with LC–MS, we finally identified 41 glutarylation sites in 24 glutarylated proteins from <i>M. tuberculosis</i>. These glutarylated proteins are involved in various cellular functions such as translation and metabolism and exhibit diverse subcellular localizations. Three common glutarylated proteins including 50S ribosomal protein L7/L12, elongation factor Tu, and dihydrolipoamide succinyltransferase are shared between <i>Escherichia coli</i> and <i>M. tuberculosis</i>. Moreover, comparison with other PTMs characterized in <i>M. tuberculosis</i>, 15 glutarylated proteins, are found to be both acetylated and succinylated. Notably, several stress-response-associated proteins including HspX are glutarylated. Our data provide the first analysis of <i>M. tuberculosis</i> lysine glutarylated proteins. Further studies on the role of the glutarylated proteins will unveil the molecular mechanisms of glutarylation underlying <i>M. tuberculosis</i> physiology and pathogenesis