Journal
CELL
Volume 155, Issue 6, Pages 1296-1308Publisher
CELL PRESS
DOI: 10.1016/j.cell.2013.10.045
Keywords
-
Categories
Funding
- National Institutes of Health [T32 GM007753, R01 AI 098637, P01 AI095208]
- Herchel Smith Graduate Fellowship of Harvard
- Wolfe-Welch Chair
- Cambridge University
Ask authors/readers for more resources
Bacteria that cause disease rely on their ability to counteract and overcome host defenses. Here, we present a genome-scale study of Mycobacterium tuberculosis (Mtb) that uncovers the bacterial determinants of surviving host immunity, sets of genes we term counteractomes. Through this analysis, we found that CD4 T cells attempt to contain Mtb growth by starving it of tryptophan-a mechanism that successfully limits infections by Chlamydia and Leishmania, natural tryptophan auxotrophs. Mtb, however, can synthesize tryptophan under stress conditions, and thus, starvation fails as an Mtb-killing mechanism. We then identify a small-molecule inhibitor of Mtb tryptophan synthesis, which converts Mtb into a tryptophan auxotroph and restores the efficacy of a failed host defense. Together, our findings demonstrate that the Mtb immune counteractomes serve as probes of host immunity, uncovering immune-mediated stresses that can be leveraged for therapeutic discovery.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available