TY  - JOUR
ID  - open3267
UR  - http://crdd.osdd.net/open/3267/
IS  - RP1038
A1  - Sarkar, Binayak
A1  - Singh, Jyotsna
A1  - Yadav, Mohit
A1  - Sharma, Priya
A1  - Sharma, Raman Deep
A1  - Singh, Shweta
A1  - Chandramouli, Aakash
A1  - Mehdiratta, Kritee
A1  - Kumar, Ashwani
A1  - Kamat, Siddhesh S
A1  - Ghorpade, Devram S
A1  - Mohanty, Debasisa
A1  - Kumar, Dhiraj
A1  - Gokhale, Rajesh S
Y1  - 2025/12//
N2  - 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 PPAR? 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 PPAR? 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.
PB  - eLife Sciences Publications, Ltd
JF  - Elife
VL  - 14
KW  - Mycobacterium tuberculosis; human; infectious disease; microbiology; mouse
TI  - PPAR? mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment
ER  -