%A Binayak Sarkar
%A Jyotsna Singh
%A Mohit Yadav
%A Priya Sharma
%A Raman Deep Sharma
%A Shweta Singh
%A Aakash Chandramouli
%A Kritee Mehdiratta
%A Ashwani Kumar
%A Siddhesh S Kamat
%A Devram S Ghorpade
%A Debasisa Mohanty
%A Dhiraj Kumar
%A Rajesh S Gokhale
%J Elife
%T PPAR? mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment
%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 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.
%N RP1038
%K Mycobacterium tuberculosis; human; infectious disease; microbiology; mouse
%V 14
%D 2025
%I eLife Sciences Publications, Ltd
%L open3267