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Biogenesis of mycobacterial cell envelope glycoconjugates
Author(s) -
Jackson Mary,
Dhouib Rabeb,
Skovierova Henrieta,
Larrouy-Maumus Gerald,
Angala Shiva K,
Wheat William H,
Pham Ha,
Gilleron Martine,
Brennan Patrick J,
Puzo Germain,
Nigou Jerome
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.358.3
Subject(s) - glycoconjugate , glycosyltransferase , biogenesis , enzyme , arabinogalactan , biochemistry , transferase , virulence , mycobacterium tuberculosis , biology , mannose , cell envelope , gene , microbiology and biotechnology , cell wall , tuberculosis , escherichia coli , medicine , pathology
The arabinogalactan (AG) of slow‐growing pathogenic Mycobacterium spp. is characterized by the presence of galactosamine (GalN) modifying some of the interior branched arabinosyl residues. We investigated the biosynthetic origin of this substituent and its role(s) in the physiology and pathogenicity of mycobacteria. We report on the discovery of the polyprenyl‐phospho‐N‐acetyl‐galactosaminyl synthase (PpgS) and the glycosyltransferase (GT) Rv3779 from Mycobacterium tuberculosis (M. tb) required, respectively, for providing and transferring the GalN substrate for the modification of AG. Disruption of either ppgS (Rv3631) or Rv3779 totally abolished the synthesis of the GalN substituent of AG in M. tb H37Rv. The identification of Rv3779 ‐ which we previously had characterized as a polyprenyl‐phospho‐mannose synthase ‐ as the GalN(Ac)transferase of the system indicates that this GT‐C enzyme is endowed with at least two distinct enzymatic activities and highlights the complexity of the GT‐C enzymes responsible for much of the biosynthesis of mycobacterial cell wall polysaccharides. Interestingly, the catalytic activity of PpgS was increased 40‐ to 50‐fold when co‐expressed with Rv3632, the encoding gene of a small putative transporter. Studies aimed at comparing the virulence and immune responses triggered by the wild‐type and GalN‐deficient strains of M. tb H37Rv are in progress.