Characterization of mycobacterial virulence genes through genetic interaction mapping
Authors
Joshi, Swati MPandey, Amit K.
Capite, Nicole
Fortune, Sarah M.
Rubin, Eric J.
Sassetti, Christopher M.
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDocument Type
Journal ArticlePublication Date
2006-07-27Keywords
AnimalsBacterial Proteins
Chromosome Mapping
DNA Transposable Elements
*Genes, Bacterial
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Mycobacterium tuberculosis
Reproducibility of Results
Tuberculosis
Virulence
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
We have previously shown that approximately 5% of the genes encoded by the genome of Mycobacterium tuberculosis are specifically required for the growth or survival of this bacterium during infection. This corresponds to hundreds of genes, most of which have no identifiable function. As a unique approach to characterize these genes, we developed a method to rapidly delineate functional pathways by identifying mutations that modify each other's phenotype, i.e., "genetic interactions". Using this method, we have defined a complex set of interactions between virulence genes in this pathogen, and find that the products of unlinked genes associate to form multisubunit transporters that are required for bacterial survival in the host. These findings implicate a previously undescribed family of transport systems in the pathogenesis of tuberculosis, and identify genes that are likely to function in the metabolism of their substrates. This method can be readily applied to other organisms at either the single pathway level, as described here, or at the system level to define quantitative genetic interaction networks.Source
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11760-5. Epub 2006 Jul 25. Link to article on publisher's site
DOI
10.1073/pnas.0603179103Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38915PubMed ID
16868085Related Resources
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.0603179103