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Use of bioinformatics to predict a function for the GS element in Mycobacterium avium subspecies paratuberculosis
Joe M Sheridan1, Tim J Bull, John Hermon-Taylor
1Department of Surgery, St George's Hospital Medical School, London, UK. jmsheridan@proteom.com
Abstract:
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 6496-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.
Insights
Mycobacterium avium subsp. Paratuberculosis (MAP) causes Johne's disease in livestock and is linked to Crohn's disease in humans. Its unique GS element may offer novel drug targets by revealing enzymes involved in cell wall biosynthesis.
Area of Science:
- Microbiology
- Immunology
- Bioinformatics
Background:
- Mycobacterium avium subsp. Paratuberculosis (MAP) causes Johne's disease in livestock and is implicated in human Crohn's disease.
- MAP belongs to the Mycobacterium avium complex (MAC), with genetic differences distinguishing pathogenic strains.
- The 6496-bp GS element is a key genetic difference between MAP and non-pathogenic MAC strains.
Purpose of the Study:
- To investigate the function of the GS element in MAP.
- To identify potential drug targets for treating MAP infections.
- To understand the role of GS-encoded enzymes in cell wall biosynthesis.
Main Methods:
- Utilized protein sequence and structural bioinformatics tools.
- Analyzed homology between GS genes and Mycobacterium avium subsp. Avium (MAA) SER2 region.
Main Results:
- Predicted that GS-encoded enzymes are involved in GDP-fucose biosynthesis.
- Hypothesized that these enzymes modify the oligosaccharide moiety of Glycolipid Phosphoglycolipid (GPL).
- GPL is a crucial cell wall component with immunomodulatory properties.
Conclusions:
- The enzymes encoded by the GS element are potential drug targets against MAP.
- Understanding GS function could lead to new therapies for livestock and human diseases.
- Targeting GPL biosynthesis pathways may inhibit pathogenic MAC growth.