Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice

Jeffery S. Cox, Bing Chen, Michael McNeil and William R. Jacobs ()
Additional contact information
Jeffery S. Cox: Howard Hughes Medical Institute, Albert Einstein College of Medicine
Bing Chen: Howard Hughes Medical Institute, Albert Einstein College of Medicine
Michael McNeil: Colorado State University
William R. Jacobs: Howard Hughes Medical Institute, Albert Einstein College of Medicine

Nature, 1999, vol. 402, issue 6757, 79-83

Abstract: Abstract Tuberculosis is the leading cause of death in the world resulting from a single bacterial infection1. Despite its enormous burden on world health, little is known about the molecular mechanisms of pathogenesis of Mycobacterium tuberculosis. Bacterial multiplication and concomitant tissue damage within an infected host, including experimentally infected mice, occurs primarily in the lungs—the favoured niche of M. tuberculosis2. Although it has been proposed that the distinctive cell wall of M. tuberculosis is important for virulence, rigorous genetic proof has been lacking. Here, using signature-tagged mutagenesis, we isolated three attenuated M. tuberculosis mutants that cannot synthesize or transport a complex, cell wall-associated lipid called phthiocerol dimycocerosate (PDIM) which is found only in pathogenic mycobacteria3,4. Two mutants have transposon insertions affecting genes implicated in PDIM synthesis; the third has a disruption in a gene encoding a large transmembrane protein required for proper subcellular localization of PDIM. Synthesis and transport of this complex lipid is only required for growth in the lung; all three mutants are unaffected for growth in the liver and spleen. This clearly shows that a lipid is required for M. tuberculosis virulence.

Date: 1999
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/47042 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:402:y:1999:i:6757:d:10.1038_47042

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/47042

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().