Journal
NATURE
Volume 431, Issue 7004, Pages 84-87Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature02837
Keywords
-
Categories
Funding
- Intramural NIH HHS [Z01 AI000783-11] Funding Source: Medline
- NIAID NIH HHS [R01 AI054338-01, R01 AI054338] Funding Source: Medline
Ask authors/readers for more resources
Fifty million new infections with Mycobacterium tuberculosis occur annually, claiming 2 - 3 million lives from tuberculosis worldwide(1). Despite the apparent lack of significant genetic heterogeneity between strains of M. tuberculosis(2,3), there is mounting evidence that considerable heterogeneity exists in molecules important in disease pathogenesis. These differences may manifest in the ability of some isolates to modify the host cellular immune response, thereby contributing to the observed diversity of clinical outcomes(4-7). Here we describe the identification and functional relevance of a highly biologically active lipid species - a polyketide synthase-derived phenolic glycolipid (PGL) produced by a subset of M. tuberculosis isolates belonging to the W-Beijing family(8) that show 'hyperlethality' in murine disease models. Disruption of PGL synthesis results in loss of this hypervirulent phenotype without significantly affecting bacterial load during disease. Loss of PGL was found to correlate with an increase in the release of the pro-inflammatory cytokines tumour-necrosis factor-alpha and interleukins 6 and 12 in vitro. Furthermore, the overproduction of PGL by M. tuberculosis or the addition of purified PGL to monocyte-derived macrophages was found to inhibit the release of these pro-inflammatory mediators in a dose-dependent manner.
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