Molecular characterization of the mycobacterial heparin-binding hemagglutinin, a mycobacterial adhesin.
Although it generally is accepted that the interaction of Mycobacterium tuberculosis with alveolar macrophages is a key step in the pathogenesis of tuberculosis, interactions with other cell types, especially epithelial cells, also may be important. In this study we describe the molecular characterization of a mycobacterial heparin-binding hemagglutinin (HBHA), a protein that functions as an adhesin for epithelial cells. The structural gene was cloned from M. tuberculosis and bacillus Calmette-Guérin, and the sequence was found to be identical between the two species. The calculated Mr was smaller than the observed Mr when analyzed by SDS/PAGE. This difference can be attributed to the Lys/Pro-rich repeats that occur at the C-terminal end of the protein and to a putative carbohydrate moiety. Glycosylation of HBHA appears to protect the protein from proteolytic degradation, which results in the removal of the C-terminal Lys/Pro-rich region responsible for binding of HBHA to sulfated carbohydrates. Evidence suggests that glycosylation is also important for HBHA-mediated hemagglutination and for certain immunologic properties of the protein. Finally, the absence of a signal peptide in the coding region of HBHA raises the possibility that this protein is not secreted via the general secretion pathway.
Laboratoire de Microbiologie Génétique et Moléculaire, Institut National de la Santé et de la Recherche Médicale U447, Institut Pasteur de Lille, 1 rue Calmette, F-59019 Lille Cedex, France.
F D
FD
Menozzi
R
R
Bischoff
E
E
Fort
M J
MJ
Brennan
C
C
Locht
D018829:Adhesins, Bacterial / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004269:DNA, Bacterial; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D006388:Hemagglutinins / Q000235:genetics*; D037102:Lectins; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000235:genetics*
D018829:Adhesins, Bacterial; D004269:DNA, Bacterial; D006388:Hemagglutinins; D037102:Lectins; C104578:heparin-binding hemagglutinin