ArticleInfection and immunity2012
Mycobacterium tuberculosis lacking all mycolic acid cyclopropanation is viable but highly attenuated and hyperinflammatory in mice.
Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 81 citations in OpenAlex.
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- A Photoactivatable Free Mycolic Acid Probe to Investigate Mycobacteria-Host Interactions.ACS infectious diseases · 2025Article
- Lipid-Centric Approaches in Combating Infectious Diseases: Antibacterials, Antifungals and Antivirals with Lipid-Associated Mechanisms of Action.Antibiotics (Basel, Switzerland) · 2023Review
- Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 ofMicrobial genomics · 2023Article
- Mouse Models forPathogens (Basel, Switzerland) · 2022Review
- Tuberculostearic Acid-Containing Phosphatidylinositols as Markers of Bacterial Burden in Tuberculosis.ACS infectious diseases · 2022Article
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- Advances in the Structural Biology, Mechanism, and Physiology of Cyclopropane Fatty Acid Modifications of Bacterial Membranes.Microbiology and molecular biology reviews : MMBR · 2022Review
- RNA Expression Analysis of Mycobacterial Methyltransferases Genes in Different Resistant Strains of Mycobacterium tuberculosis.Iranian biomedical journal · 2022Article
- MadR mediates acyl CoA-dependent regulation of mycolic acid desaturation in mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cyclopropane Fatty Acids Are Important forInfection and immunity · 2022Article
- Fragment-Based Ligand Discovery Applied to the Mycolic Acid Methyltransferase Hma (MmaA4) fromPharmaceuticals (Basel, Switzerland) · 2021Article
- Profiles of Volatile Biomarkers Detect Tuberculosis from Skin.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Phylogenomic Reappraisal of Fatty Acid Biosynthesis, Mycolic Acid Biosynthesis and Clinical Relevance Among Members of the GenusFrontiers in microbiology · 2021Article
- A Phenotypic Characterization of Two Isolates of a Multidrug-Resistant Outbreak Strain ofBioMed research international · 2020Article
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- Transposon libraries identify novel Mycobacterium bovis BCG genes involved in the dynamic interactions required for BCG to persist during in vivo passage in cattle.BMC genomics · 2019Article
- A novel mutation alters the stability of PapA2 resulting in the complete abrogation of sulfolipids in clinical mycobacterial strains.FASEB bioAdvances · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Mycolic acids, the major lipid of the Mycobacterium tuberculosis cell wall, are modified by cyclopropane rings, methyl branches, and oxygenation through the action of eight S-adenosylmethionine (SAM)-dependent mycolic acid methyltransferases (MAMTs), encoded at four genetic loci. Mycolic acid modification has been shown to be important for M. tuberculosis pathogenesis, in part through effects on the inflammatory activity of trehalose dimycolate (cord factor). Studies using the MAMT inhibitor dioctylamine have suggested that the MAMT enzyme class is essential for M. tuberculosis viability. However, it is unknown whether a cyclopropane-deficient strain of M. tuberculosis would be viable and what the effect of cyclopropane deficiency on virulence would be. We addressed these questions by creating and characterizing M. tuberculosis strains lacking all functional MAMTs. Our results show that M. tuberculosis is viable either without cyclopropanation or without cyclopropanation and any oxygenated mycolates. Characterization of these strains revealed that MAMTs are required for acid fastness and resistance to detergent stress. Complete lack of cyclopropanation confers severe attenuation during the first week after aerosol infection of the mouse, whereas complete loss of MAMTs confers attenuation in the second week of infection. Characterization of immune responses to the cyclopropane- and MAMT-deficient strains indicated that the net effect of mycolate cyclopropanation is to dampen host immunity. Taken together, our findings establish the immunomodulatory function of the mycolic acid modification pathway in pathogenesis and buttress this enzyme class as an attractive target for antimycobacterial drug development.
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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.