Use of Bioinformatics to Predict a Function for the GS Element in Mycobacterium avium Subspecies paratuberculosis

Mycobacterium avium subsp. paratuberculosis (MAP) is a member of the Mycobacterium avium complex (MAC) and causes the inflammatory bowel disease, Johne’s disease, in livestock. MAP has also been implicated as the causative agent of a similar disease, Crohn’s disease, in humans. One of three major genetic differences between MAP and non-pathogenic MAC is the 6,496-bp GS element. Based on the output from freely available protein sequence and structural bioinformatics tools, and the close homology of GS genes with the ser2 region of the closely related Mycobacterium avium subsp. avium (MAA), we predict that GS encoded enzymes are involved in the biosynthesis of GDP-fucose, and the addition to, and modification of fucose on, the oligosaccharide moiety of GPL. GPL is a major constituent of the cell wall of the MAC and has immunomodulatory properties. Therefore, the enzymes involved in its synthesis may provide novel drug targets against MAP and other pathogenic MAC members.