Sarkar, Binayak and Singh, Jyotsna and Yadav, Mohit and Sharma, Priya and Sharma, Raman Deep and Singh, Shweta and Chandramouli, Aakash and Mehdiratta, Kritee and Kumar, Ashwani and Kamat, Siddhesh S and Ghorpade, Devram S and Mohanty, Debasisa and Kumar, Dhiraj and Gokhale, Rajesh S (2025) PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment. Elife, 14 (RP1038).
Full text not available from this repository.Abstract
Mycobacterium tuberculosis (Mtb) infection of the lungs, besides producing prolonged cough with mucus, also causes progressive fatigue and cachexia with debilitating loss of muscle mass. While anti-tuberculosis (TB) drug therapy is directed toward eliminating bacilli, the treatment regimen ignores the systemic pathogenic derailments that probably dictate TB-associated mortality and morbidity. Presently, it is not understood whether Mtb spreads to metabolic organs and brings about these impairments. Here, we show that Mtb creates a replication-conducive milieu of lipid droplets in hepatocytes by upregulating transcription factor PPARγ and scavenging lipids from the host cells. In hepatocytes, Mtb shields itself against the common anti-TB drugs by inducing drug-metabolizing enzymes. Infection of the hepatocytes in the in vivo aerosol mice model can be consistently observed post-week, 4 along with enhanced expression of PPARγ and drug-metabolizing enzymes. Moreover, histopathological analysis indeed shows the presence of Mtb in hepatocytes along with granuloma-like structures in human biopsied liver sections. Hepatotropism of Mtb during the chronic infectious cycle results in immuno-metabolic dysregulation that could magnify local and systemic pathogenicity, altering clinical presentations.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Mycobacterium tuberculosis; human; infectious disease; microbiology; mouse |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 01 Feb 2026 13:49 |
| Last Modified: | 01 Feb 2026 13:49 |
| URI: | http://crdd.osdd.net/open/id/eprint/3267 |
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