Cited by 295Tuberculosis Research and EpidemiologyImmune responses and vaccinationsLipid metabolism and biosynthesis

Mycobacterium tuberculosis-Driven Targeted Recalibration of Macrophage Lipid Homeostasis Promotes the Foamy Phenotype

Open access
Singh, Varshneya, Jamwal, Shilpa, Jain, Ritu, Verma, Priyanka, Gokhale, Rajesh, Rao, Kanury V.S.·2012·Cell Host & Microbe

Abstract

Upon infection, Mycobacterium tuberculosis (Mtb) metabolically alters the macrophage to create a niche that is ideally suited to its persistent lifestyle. Infected macrophages acquire a "foamy" phenotype characterized by the accumulation of lipid bodies (LBs), which serve as both a source of nutrients and a secure niche for the bacterium. While the functional significance of the foamy phenotype is appreciated, the biochemical pathways mediating this process are understudied. We found that Mtb induces the foamy phenotype via targeted manipulation of host cellular metabolism to divert the glycolytic pathway toward ketone body synthesis. This dysregulation enabled feedback activation of the anti-lipolytic G protein-coupled receptor GPR109A, leading to perturbations in lipid homeostasis and consequent accumulation of LBs in the macrophage. ESAT-6, a secreted Mtb virulence factor, mediates the enforcement of this feedback loop. Finally, we demonstrate that pharmacological targeting of pathways mediating this host-pathogen metabolic crosstalk provides a potential strategy for developing tuberculosis chemotherapy.

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Crossref · 10.1016/j.chom.2012.09.012

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  • M. tuberculosis diverts host metabolism from a glycolytic pathway toward ketone biosynthesis via the mycobacterial virulence factor ESAT-6.

    “This is done by diversion of the host metabolism from a glycolytic pathway toward ketone biosynthesis, which is mediated by the mycobacterial virulence factor ESAT-6 (90).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [90]

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Authors
Singh, V., Jamwal, S., Jain, R., Verma, P., Gokhale, R., & Rao, K. V. S.
Affiliations
  • International Centre for Genetic Engineering and Biotechnology (IN)
  • National Institute of Immunology (IN)
  • Institute of Genomics and Integrative Biology (IN)
Corresponding author
Rao, Kanury V.S.
Venue
Cell Host & Microbe
Publisher
Elsevier BV
Published
2012-11
Volume
12
Issue
5
Pages
669-681
ISSN
1931-3128 (ISSN-L)
OpenAlex
W1978993402
Cited by
295
References
32
Citations by year
2026: 11 · 2025: 26 · 2024: 17 · 2023: 22 · 2022: 16 · 2021: 27 · 2020: 25 · 2019: 24 · 2018: 19 · 2017: 26 · 2016: 29 · 2015: 24 · 2014: 12 · 2013: 15 · 2012: 2
FWCI
11.71
Type
journal article
Language
en
Open access
Locations
  • Cell Host & Microbe (publishedVersion)
  • PubMed (publishedVersion)
Funders
Department of Biotechnology, Ministry of Science and Technology, India
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
Mycobacterium tuberculosis, tuberculosis, lipid droplets, foam cells, ketone body synthesis, glycolysis, GPR109A, ESAT-6, tuberculosis chemotherapy
MeSH terms
Sterol O-Acyltransferase 2, Acetyl-CoA C-Acetyltransferase, Animals, Antigens, Bacterial, Bacterial Proteins, Sterol O-Acyltransferase, Female, Homeostasis, Humans, Hydroxybutyrates, Ketone Bodies, Leukocytes, Mononuclear, Macrophages, Mice, Inbred BALB C, Mycobacterium tuberculosis, Phenotype, Receptors, Nicotinic, Autocrine Communication, Receptors, G-Protein-Coupled, Cell Line, Tumor, Lipid Metabolism, Mice

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