The MPB83 antigen from Mycobacterium bovis contains O-linked mannose and (1-->3)-mannobiose moieties.
Mycobacterium tuberculosis and Mycobacterium bovis, the causative agents of human and bovine tuberculosis, have been reported to express a range of surface and secreted glycoproteins, although only one of these has been subjected to detailed structural analysis. We describe the use of a genetic system, in conjunction with lectin binding, to characterize the points of attachment of carbohydrate moieties to the polypeptide backbone of a second mycobacterial glycoprotein, antigen MPB83 from M. bovis. Biochemical and structural analysis of the native MPB83 protein and derived peptides demonstrated the presence of 3 mannose units attached to two threonine residues. Mannose residues were joined by a (1 --> 3) linkage, in contrast to the (1 --> 2) linkage previously observed in antigen MPT32 from M. tuberculosis and the (1 --> 2) and (1 --> 6) linkages in other mycobacterial glycolipids and polysaccharides. The identification of glycosylated antigens within the M. tuberculosis complex raises the possibility that the carbohydrate moiety of these glycoproteins might be involved in pathogenesis, either by interaction with mannose receptors on host cells, or as targets or modulators of the cell-mediated immune response. Given such a possibility characterization of mycobacterial glycoproteins is a step toward understanding their functional role and elucidating the mechanisms of mycobacterial glycosylation.
Michell
Stephen L
SL
TB Research Group, Department of Bacterial Diseases, Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK. slmichell@dstl.gov.uk
Whelan
Adam O
AO
Wheeler
Paul R
PR
Panico
Maria
M
Easton
Richard L
RL
Etienne
A Tony
AT
Haslam
Stuart M
SM
Dell
Anne
A
Morris
Howard R
HR
Reason
Andrew J
AJ
Herrmann
Jean Louis
JL
Young
Douglas B
DB
Hewinson
R Glyn
RG
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D006031:Glycosylation; D008358:Mannose / Q000737:chemistry; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009163:Mycobacterium bovis / Q000276:immunology*
D008358:Mannose