Characterization of Mycobacterial Virulence Genes Through Genetic Interaction Mapping

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Jul 27

PMID 16868085

Citations 102

Authors

Swati M Joshi

Amit K Pandey

Nicole Capite

Sarah M Fortune

Eric J Rubin

Christopher M Sassetti

Affiliations

Soon will be listed here.

Abstract

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.

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