Glycobiology Advance Access originally published online on January 29, 2007
Glycobiology 2007 17(6):35R-56R; doi:10.1093/glycob/cwm010
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The glycosyltransferases of Mycobacterium tuberculosis—roles in the synthesis of arabinogalactan, lipoarabinomannan, and other glycoconjugates
3 Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523
4 Unité de Génétique Mycobactérienne, Institut Pasteur, 75724 Paris Cedex 15, France
1 To whom correspondence should be addressed; Tel: +1-970 491 6700; Fax: 970 491 1815; e-mail: patrick.brennan{at}colostate.edu
Received on October 20, 2006; revised on January 22, 2007; accepted on January 23, 2007
Several human pathogens are to be found within the bacterial genus Mycobacterium, notably Mycobacterium tuberculosis, the causative agent of tuberculosis, one of the most threatening of human infectious diseases, with an annual lethality of about two million people. The characteristic mycobacterial cell envelope is the dominant feature of the biology of M. tuberculosis and other mycobacterial pathogens, based on sugars and lipids of exceptional structure. The cell wall consists of a peptidoglycan-arabinogalactan-mycolic acid complex beyond the plasma membrane. Free-standing lipids, lipoglycans, and proteins intercalate within this complex, complement the mycolic acid monolayer and may also appear in a capsular-like arrangement. The consequences of these structural oddities are an extremely robust and impermeable cell envelope. This review reflects on these entities from the perspective of their synthesis, particularly the structural and functional aspects of the glycosyltransferases (GTs) of M. tuberculosis, the dominating group of enzymes responsible for the terminal stages of their biosynthesis. Besides the many nucleotide-sugar dependent GTs with orthologs in prokaryotes and eukaryotes, M. tuberculosis and related species of the order Actinomycetales, in light of the highly lipophilic environment prevailing within the cell envelope, carry a significant number of GTs of the GT-C class dependent on polyprenyl-phosphate-linked sugars. These are of special emphasis in this review.
Key words: Mycobacterium / glycosyltransferase / classification / arabinogalactan / lipoarabinomannan
2 Present address: Centre for Molecular Microbiology and Infection, Imperial College London, London SW7 2AZ, UK
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