Comparative expression studies of a complex phenotype: cord formation in Mycobacterium tuberculosis

The aggregation of mycobacteria into structures known as cords is an intrinsic property of the human tubercle bacillus. This property is thought to be determined by the lipid composition of the bacterial cell surface and may contribute to the virulence of the organism. Using microarray technology, we compared the pattern of gene expression of H37Rv, a virulent, cording strain of Mycobacterium tuberculosis, with H37Ra, an avirulent, non-cording strain derived from the same original patient isolate, under five different nutrient combinations and growth conditions. Under all of these conditions, H37Rv formed cords and H37Ra did not. By focusing our analysis only on genes that were differentially expressed under all conditions, we hoped to enrich the resulting gene list for genes associated with cording. We identified 22 genes that were consistently expressed at higher levels in H37Rv than in H37Ra under all conditions tested. Genes involved in lipid metabolism and the cell membrane were significantly enriched in our gene list, indicating that the cell wall and the cell membrane may be the major sites of difference between these two strains. This work represents a new strategy for enriching gene lists for relevant genes, which may also be applicable for other types of problems.