PT  - JOURNAL ARTICLE
AU  - Eliza J.R. Peterson
AU  - Rebeca Bailo
AU  - Alissa C. Rothchild
AU  - Mario Arrieta-Ortiz
AU  - Amardeep Kaur
AU  - Min Pan
AU  - Dat Mai
AU  - Charlotte Cooper
AU  - Alan Aderem
AU  - Apoorva Bhatt
AU  - Nitin S. Baliga
TI  - An essential mycolate remodeling program for mycobacterial adaptation in host cells
AID  - 10.1101/354431
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 354431
4099  - http://biorxiv.org/content/early/2018/06/22/354431.short
4100  - http://biorxiv.org/content/early/2018/06/22/354431.full
AB  - 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 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/A2 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.One Sentence Summary Novel technology (Path-seq) discovers cell wall remodeling program during Mycobacterium tuberculosis infection of macrophages