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Lysine Acetylation of Translation Initiation Factor IF-2 Mediated by Mycobacterial Acetyltransferase Eis

ABSTRACT: In our study, we employed the non-pathogenic Mycobacterium smegmatis as a model organism and applied a multi-omics approach to elucidate the substrate specificity and regulatory function of the mycobacterial acetyltransferase Eis. Through the integration of TMT-based acetyl-proteomics, dimethyl labeling-based acetyl-proteomics, and protein interactome analyses, we identified lysine 509 of the translation initiation factor IF-2 (infB), which is involved in ribosomal function, as a novel substrate of Eis. Acetylation at K509 was found to inhibit the GTPase activity of infB, leading to a decrease in the biosynthesis of nascent proteins. Furthermore, we demonstrated that Eis-mediated acetylation of infB reduced the tolerance of bioengineered M. smegmatis strain to the ribosome-targeting antibiotic clarithromycin and increased the production of inflammatory cytokines infected in the macrophage THP-1 cell line and mouse kidney. Our findings elucidate the Eis-infB regulatory axis, highlighting the critical roles of infB K509 acetylation in modulating mycobacterial homeostasis, ribosomal function, and host immune responses.

ORGANISM(S): Mycolicibacterium Smegmatis Mc2 51

SUBMITTER: Junyu Xu

PROVIDER: PXD076847 | iProX | Fri Apr 10 00:00:00 BST 2026

REPOSITORIES: iProX

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