Bioinformatics and protein modelling of the GS element of Mycobacterium avium subsp. paratuberculosis (MAP) and GS-encoded proteins as drug targets and vaccine components

Abstract

AIM: To determine the function and cellular localization of GS encoded proteins and to assess their potential as drug targets and vaccine components.

METHODS: Bioinformatics software was used to predict the function of GS-encoded proteins and their location within MAP. Protein modelling software was used to build protein structures.

RESULTS: The gene gsa is a truncated glycosyl transferase and probably nonfunctional. gsbA and gsbB produce GDP fucose which is methylated by gsc and acetylated by mpa. gsd is a fucosyl transferase which attaches fucose to subterminal rhamnose on cell surface glycopeptidolipid. gsa, gsbA and gsbB- and gsc are located within the cytoplasm. mpa is embedded in the plasma membrane with 10 transmembrane regions and a conspicuous extracellular loop. gsd is lipid linked and predicted to localize to the microbial cell surface.

CONCLUSION: GS encodes the biosynthetic machinery to give -MAP a surface coat of methylated and acetylated fucose which may contribute to its protease-resistant nature and ability to minimize immune recognition. The gsbA/gsbB-operon and gsd are promising drug targets and gsd is a good candidate component of a new class of anti-MAP vaccines.

Key Words: Mycobacterium avium; Paratuberculosis; Glycosyltransferase; Vaccines; Genes; Protease inhibitors