Path-seq identifies an essential mycolate remodeling program for mycobacterial host adaptation
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
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.
|Number of pages||19|
|Journal||Molecular Systems Biology|
|Publication status||Published - 1 Mar 2019|
- gene regulatory networks, host–pathogen interactions, Mycobacterium tuberculosis, Path-seq, systems biology