ArticlePLoS pathogens2008
Mycolic acid modification by the mmaA4 gene of M. tuberculosis modulates IL-12 production.
Article in PLoS pathogens, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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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.
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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.
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Who cites it
54 citing papers in PubMed, 104 citations in OpenAlex.
- Role of Tumor Necrosis Factor in Tuberculosis.Biomolecules · 2025Review
- Comparative transcriptomic signatures of virulent and attenuatedFrontiers in cellular and infection microbiology · 2025Article
- HadBD dehydratase from Mycobacterium tuberculosis fatty acid synthase type II: A singular structure for a unique function.Protein science : a publication of the Protein Society · 2024Article
- Effect of Mycolic Acids on Host Immunity and Lipid Metabolism.International journal of molecular sciences · 2023Review
- Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 ofMicrobial genomics · 2023Article
- Mouse Models forPathogens (Basel, Switzerland) · 2022Review
- Resistance and Susceptibility Immune Factors at Play duringPathogens (Basel, Switzerland) · 2022Review
- Article
- Fragment-Based Ligand Discovery Applied to the Mycolic Acid Methyltransferase Hma (MmaA4) fromPharmaceuticals (Basel, Switzerland) · 2021Article
- Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives.International journal of molecular sciences · 2021Article
- Phylogenomic Reappraisal of Fatty Acid Biosynthesis, Mycolic Acid Biosynthesis and Clinical Relevance Among Members of the GenusFrontiers in microbiology · 2021Article
- Discovery of a novel dehydratase of the fatty acid synthase type II critical for ketomycolic acid biosynthesis and virulence of Mycobacterium tuberculosis.Scientific reports · 2020Article
- Simvastatin Enhances the Immune Response AgainstFrontiers in microbiology · 2019Article
- Mycobacterial Evolution Intersects With Host Tolerance.Frontiers in immunology · 2019Review
- Effect of Homocysteine on Biofilm Formation by Mycobacteria.Indian journal of microbiology · 2018Article
- Potential Effect of Statins onJournal of immunology research · 2018Review
- Expression of a recombinant, 4'-Phosphopantetheinylated, active M. tuberculosis fatty acid synthase I in E. coli.PloS one · 2018Article
- Molecular basis of mycobacterial survival in macrophages.Cellular and molecular life sciences : CMLS · 2017Review
- Sensing Lipids with Mincle: Structure and Function.Frontiers in immunology · 2017Review
- Inflammatory Properties and Adjuvant Potential of Synthetic Glycolipids Homologous to Mycolate Esters of the Cell Wall of Mycobacterium tuberculosis.Journal of innate immunity · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Mycobacterium tuberculosis has evolved many strategies to evade elimination by the host immune system, including the selective repression of macrophage IL-12p40 production. To identify the M. tuberculosis genes responsible for this aspect of immune evasion, we used a macrophage cell line expressing a reporter for IL-12p40 transcription to screen a transposon library of M. tuberculosis for mutants that lacked this function. This approach led to the identification of the mmaA4 gene, which encodes a methyl transferase required for introducing the distal oxygen-containing modifications of mycolic acids, as a key locus involved in the repression of IL-12p40. Mutants in which mmaA4 (hma) was inactivated stimulated macrophages to produce significantly more IL-12p40 and TNF-alpha than wild-type M. tuberculosis and were attenuated for virulence. This attenuation was not seen in IL-12p40-deficient mice, consistent with a direct linkage between enhanced stimulation of IL-12p40 by the mutant and its reduced virulence. Treatment of macrophages with trehalose dimycolate (TDM) purified from the DeltammaA4 mutant stimulated increased IL-12p40, similar to the increase observed from DeltammaA4 mutant-infected macrophages. In contrast, purified TDM isolated from wild-type M. tuberculosis inhibited production of IL-12p40 by macrophages. These findings strongly suggest that M. tuberculosis has evolved mmaA4-derived mycolic acids, including those incorporated into TDM to manipulate IL-12-mediated immunity and virulence.
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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.