Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 199, Issue 9, Pages 1191-1199Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20031956
Keywords
isoniazid; macrophage; Mycobacterium tuberculosis; cell wall; metabolism
Categories
Funding
- Wellcome Trust Funding Source: Medline
Ask authors/readers for more resources
Mycolic acids represent a major component of the unique cell wall of mycobacteria. Mycolic acid biosynthesis is inhibited by isoniazid, a key frontline antitubercular drug that is inactivated by mycobacterial and human arylamine NI-acetyltransferase (NAT). We show that an in-frame deletion of Mycobacterium bovis BCG nat results in delayed entry into log phase, altered morphology, altered cell wall lipid composition, and increased intracellular killing by macrophages. In particular, deletion of nat perturbs biosynthesis of mycolic acids and their derivatives and increases susceptibility of M. bovis BCG to antibiotics that permeate the cell wall. Phenotypic traits are fully complemented by introduction of Mycobacterium tuberculosis nat. We infer from our findings that NAT is critical to normal mycolic acid synthesis and hence other derivative cell wall components and represents a novel target for antituberculosis therapy. In addition, this is the first report of an endogenous role for NAT in mycobacteria.
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