ArticlePLoS pathogens2014
Mycobacterium tuberculosis Hip1 modulates macrophage responses through proteolysis of GroEL2.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Seryl phosphorylation modulates chaperonin function of Mycobacterial chaperonin, Cpn60.1.Cell stress & chaperones · 2026Article
- Functional impact of a conservative missense mutation in the Mycobacterium bovis BCG Moreau heat shock response regulator hrcA gene.BMC microbiology · 2026Article
- Exploring the Protein Landscape of Dormant Mycobacterium tuberculosis Through In Vitro Functional Studies.Advances in experimental medicine and biology · 2026Review
- Discovery of highly potent α-keto ester-based peptidomimetic inhibitors of the Hip1 protease for the treatment ofEuropean journal of medicinal chemistry reports · 2025Article
- Review
- Activation and evasion of inflammasomes during viral and microbial infection.Cellular and molecular life sciences : CMLS · 2025Review
- Roles of Lipolytic enzymes inFrontiers in microbiology · 2024Review
- Detection of a target protein (GroEl2) in Mycobacterium tuberculosis using a derivative of 1,2,4-triazolethiols.Molecular diversity · 2022Article
- Article
- Interaction of Mycobacteria With Host Cell Inflammasomes.Frontiers in immunology · 2022Review
- Mycobacterium tuberculosis inhibits the NLRP3 inflammasome activation via its phosphokinase PknF.PLoS pathogens · 2021Article
- Chemiluminescent Protease Probe for Rapid, Sensitive, and Inexpensive Detection of LiveACS central science · 2021Article
- Advancing Adjuvants forFrontiers in immunology · 2021Review
- Fighting Persistence: How Chronic Infections with Mycobacterium tuberculosis Evade T Cell-Mediated Clearance and New Strategies To Defeat Them.Infection and immunity · 2020Review
- Host Cell Targets of Released Lipid and Secreted Protein Effectors ofFrontiers in cellular and infection microbiology · 2020Review
- Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice.Scientific reports · 2019Article
- Immunology ofMicrobiology spectrum · 2019Review
- MTS1338, A SmallFrontiers in cellular and infection microbiology · 2019Article
- Mycobacterium tuberculosis GroEL2 Modulates Dendritic Cell Responses.Infection and immunity · 2018Article
- Regulation of Three Virulence Strategies of Mycobacterium tuberculosis: A Success Story.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) employs multiple strategies to evade host immune responses and persist within macrophages. We have previously shown that the cell envelope-associated Mtb serine hydrolase, Hip1, prevents robust macrophage activation and dampens host pro-inflammatory responses, allowing Mtb to delay immune detection and accelerate disease progression. We now provide key mechanistic insights into the molecular and biochemical basis of Hip1 function. We establish that Hip1 is a serine protease with activity against protein and peptide substrates. Further, we show that the Mtb GroEL2 protein is a direct substrate of Hip1 protease activity. Cleavage of GroEL2 is specifically inhibited by serine protease inhibitors. We mapped the cleavage site within the N-terminus of GroEL2 and confirmed that this site is required for proteolysis of GroEL2 during Mtb growth. Interestingly, we discovered that Hip1-mediated cleavage of GroEL2 converts the protein from a multimeric to a monomeric form. Moreover, ectopic expression of cleaved GroEL2 monomers into the hip1 mutant complemented the hyperinflammatory phenotype of the hip1 mutant and restored wild type levels of cytokine responses in infected macrophages. Our studies point to Hip1-dependent proteolysis as a novel regulatory mechanism that helps Mtb respond rapidly to changing host immune environments during infection. These findings position Hip1 as an attractive target for inhibition for developing immunomodulatory therapeutics against Mtb.
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Registered trials
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.