Project description:The success of Mycobacterium tuberculosis (MTB) stems from its ability to remain hidden from the immune system within macrophages. Here, we report a new technology (Path-seq) to sequence miniscule amounts of MTB transcripts within up to million-fold excess host RNA Using Path-seq and regulatory network analyses, we have discovered a novel transcriptional program for in vivo mycobacterial cell wall remodeling when the pathogen infects alveolar macrophages in mice. We have discovered that MadR transcriptionally modulates two mycolic acid desaturases desA1/desA2 to initially promote cell wall remodeling upon in vitro macrophage infection and, subsequently, reduces mycolate biosynthesis upon entering dormancy. We demonstrate that disrupting MadR program is lethal to diverse mycobacteria making this evolutionarily conserved regulator a prime antitubercular target for both early and late stages of infection.
Project description:Comparison of transcriptional differences (RNA-seq) between induced and uninduced overexpression of MSMEG_0916 in Mycobacterium smegmatis
Project description:Study of the DNA binding sites of the transcriptional regulator MSMEG_0916 through chromatin immunoprecipitation couple with deep sequenicng (ChIP-seq) and induced or uninduced overexpression of MSMEG_0916 in Mycobacterium smegmatis
Project description:Tuberculosis and non-tuberculous mycobacterial (NTM) diseases are infections caused by Mycobacterium tuberculosis and non-tuberculous mycobacteria, leading to the formation of granulomatous lesions with caseous necrosis in the lungs. We applied spatial transcriptomics at single-cell resolution (CosMx Spatial Molecular Imaging) to human lung samples from patients with mycobacterial infections. RNA-seq was also performed on the samples.