ArticleProceedings of the National Academy of Sciences of the United States of America2012
Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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116 citing papers in PubMed, 198 citations in OpenAlex.
- Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies ofMedComm · 2026Review
- Bioorthogonal Click Chemistry for Antibody-Free Profiling of Acetylation, Propionylation, and Butyrylation inACS infectious diseases · 2026Article
- A Comprehensive Review of Genetic Mechanisms ofInfection and drug resistance · 2026Review
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Regulatory roles of MKP7/DUSP16 in cancer.Medical oncology (Northwood, London, England) · 2025Review
- The role of TRIM proteins in the pathogenesis of mycobacterium tuberculosis.Biology direct · 2025Review
- Rv1899c, an HDAC1-ZBTB25-Interacting Protein ofInternational journal of molecular sciences · 2025Article
- Metabolic reprogramming of immune cells in the battle against intracellular bacterial chronic infections: novel mechanisms and breakthroughs.Molecular biology reports · 2025Review
- The pathway of autophagy in the epigenetic landscape ofAutophagy · 2025Review
- The acetyltransferase CysE modulates virulence and drug resistance of Mycobacterium tuberculosis by interfering with oxidative stress responses.Communications biology · 2025Article
- SMURF2 inhibits autophagic control ofbioRxiv : the preprint server for biology · 2025Article
- Identification ofMicrobiology spectrum · 2025Article
- NProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting Autophagy as a Strategy for Developing New Host-Directed Therapeutics Against Nontuberculous Mycobacteria.Pathogens (Basel, Switzerland) · 2025Review
- Insights into Autophagy in Microbiome Therapeutic Approaches for Drug-Resistant Tuberculosis.Cells · 2025Review
- Suppressing Mycobacterium tuberculosis virulence and drug resistance by targeting Eis protein through computational drug discovery.Molecular diversity · 2025Article
- Dysregulation of the JNK signaling pathway in tuberculosis: mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2025Review
- Overcoming aminoglycoside antibiotic resistance inIn silico pharmacology · 2025Article
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56 more citing papers are in PubMed but not listed here.
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16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intracellular pathogen Mycobacterium tuberculosis (Mtb) causes tuberculosis. Enhanced intracellular survival (Eis) protein, secreted by Mtb, enhances survival of Mycobacterium smegmatis (Msm) in macrophages. Mtb Eis was shown to suppress host immune defenses by negatively modulating autophagy, inflammation, and cell death through JNK-dependent inhibition of reactive oxygen species (ROS) generation. Mtb Eis was recently demonstrated to contribute to drug resistance by acetylating multiple amines of aminoglycosides. However, the mechanism of enhanced intracellular survival by Mtb Eis remains unanswered. Therefore, we have characterized both Mtb and Msm Eis proteins biochemically and structurally. We have discovered that Mtb Eis is an efficient N(ε)-acetyltransferase, rapidly acetylating Lys55 of dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7), a JNK-specific phosphatase. In contrast, Msm Eis is more efficient as an N(α)-acetyltransferase. We also show that Msm Eis acetylates aminoglycosides as readily as Mtb Eis. Furthermore, Mtb Eis, but not Msm Eis, inhibits LPS-induced JNK phosphorylation. This functional difference against DUSP16/MKP-7 can be understood by comparing the structures of two Eis proteins. The active site of Mtb Eis with a narrow channel seems more suitable for sequence-specific recognition of the protein substrate than the pocket-shaped active site of Msm Eis. We propose that Mtb Eis initiates the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation by acetylating DUSP16/MKP-7. Our work thus provides insight into the mechanism of suppressing host immune responses and enhancing mycobacterial survival within macrophages by Mtb Eis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.