ArticleThe Journal of clinical investigation2022
Macrophage global metabolomics identifies cholestenone as host/pathogen cometabolite present in human Mycobacterium tuberculosis infection.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Macrophage signaling and function are regulated by distinct sterol biochemistries.Journal of lipid research · 2026Article
- ARNA (New York, N.Y.) · 2026Article
- Shared and distinct responses of human and murine alveolar macrophages and monocyte-derived macrophages to Mycobacterium tuberculosis.ImmunoHorizons · 2025Article
- Backtracking metabolic dynamics in single cells predicts bacterial replication in human macrophages.Nature communications · 2025Article
- Activation of nuclear receptors correlates with tuberculosis severity and is a target for host-directed therapy.Frontiers in cellular and infection microbiology · 2025Article
- Host Circulating Immunometabolism-Associated Biomarkers for Early Diagnosis of Active Tuberculosis: Multi-Omics Screening with Experimental Validation.Journal of inflammation research · 2025Article
- Epigenetic programming of host lipid metabolism associated with resistance to TST/IGRA conversion after exposure tomSystems · 2024Article
- The role of cholesterol and its oxidation products in tuberculosis pathogenesis.Immunometabolism (Cobham, Surrey) · 2024Review
- Urinary markers of Mycobacterium tuberculosis and dysbiosis in paediatric tuberculous meningitis cases undergoing treatment.Gut pathogens · 2024Article
- Epigenetic programming of host lipid metabolism associates with resistance to TST/IGRA conversion after exposure tobioRxiv : the preprint server for biology · 2024Article
- The uncharted territory of host-pathogen interaction in tuberculosis.Frontiers in immunology · 2024Review
- Rifampicin drug resistance and host immunity in tuberculosis: more than meets the eye.Trends in immunology · 2023Review
- Accumulation of oxysterols in the erythrocytes of COVID-19 patients as a biomarker for case severity.Respiratory research · 2023Article
- Atg8ylation as a host-protective mechanism againstFrontiers in tuberculosis · 2023Article
- Biomarker discovery for tuberculosis using metabolomics.Frontiers in molecular biosciences · 2023Review
- Culture independent markers of nontuberculous mycobacterial (NTM) lung infection and disease in the cystic fibrosis airway.Tuberculosis (Edinburgh, Scotland) · 2023Article
- Immune evasion and provocation by Mycobacterium tuberculosis.Nature reviews. Microbiology · 2022Review
- Article
- Non-Coding RNAs in Tuberculosis Epidemiology: Platforms and Approaches for Investigating the Genome's Dark Matter.International journal of molecular sciences · 2022Review
- Understanding the contribution of metabolism toFrontiers in cellular and infection microbiology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mycobacterium tuberculosis (M. tuberculosis) causes an enormous burden of disease worldwide. As a central aspect of its pathogenesis, M. tuberculosis grows in macrophages, and host and microbe influence each other's metabolism. To define the metabolic impact of M. tuberculosis infection, we performed global metabolic profiling of M. tuberculosis-infected macrophages. M. tuberculosis induced metabolic hallmarks of inflammatory macrophages and a prominent signature of cholesterol metabolism. We found that infected macrophages accumulate cholestenone, a mycobacterial-derived, oxidized derivative of cholesterol. We demonstrated that the accumulation of cholestenone in infected macrophages depended on the M. tuberculosis enzyme 3β-hydroxysteroid dehydrogenase (3β-Hsd) and correlated with pathogen burden. Because cholestenone is not a substantial human metabolite, we hypothesized it might be diagnostic of M. tuberculosis infection in clinical samples. Indeed, in 2 geographically distinct cohorts, sputum cholestenone levels distinguished subjects with tuberculosis (TB) from TB-negative controls who presented with TB-like symptoms. We also found country-specific detection of cholestenone in plasma samples from M. tuberculosis-infected subjects. While cholestenone was previously thought to be an intermediate required for cholesterol degradation by M. tuberculosis, we found that M. tuberculosis can utilize cholesterol for growth without making cholestenone. Thus, the accumulation of cholestenone in clinical samples suggests it has an alternative role in pathogenesis and could be a clinically useful biomarker of TB infection.
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Registered trials
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