%0 Journal Article
%A Sarkar, Binayak
%A Singh, Jyotsna
%A Yadav, Mohit
%A Sharma, Priya
%A Sharma, Raman Deep
%A Singh, Shweta
%A Chandramouli, Aakash
%A Mehdiratta, Kritee
%A Kumar, Ashwani
%A Kamat, Siddhesh S
%A Ghorpade, Devram S
%A Mohanty, Debasisa
%A Kumar, Dhiraj
%A Gokhale, Rajesh S
%D 2025
%F open:3267
%I eLife Sciences Publications, Ltd
%J Elife
%K Mycobacterium tuberculosis; human; infectious disease; microbiology; mouse
%N RP1038
%T PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment
%U http://crdd.osdd.net/open/3267/
%V 14
%X 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.