@article{open3267,
          volume = {14},
          number = {RP1038},
           month = {December},
          author = {Binayak Sarkar and Jyotsna Singh and Mohit Yadav and Priya Sharma and Raman Deep Sharma and Shweta Singh and Aakash Chandramouli and Kritee Mehdiratta and Ashwani Kumar and Siddhesh S Kamat and Devram S Ghorpade and Debasisa Mohanty and Dhiraj Kumar and Rajesh S Gokhale},
           title = {PPAR{\ensuremath{\gamma}} mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment},
       publisher = {eLife Sciences Publications, Ltd},
         journal = {Elife},
            year = {2025},
        keywords = {Mycobacterium tuberculosis; human; infectious disease; microbiology; mouse},
             url = {http://crdd.osdd.net/open/3267/},
        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 PPAR{\ensuremath{\gamma}} 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{\ensuremath{\gamma}} 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.}
}