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.
Menozzi
F D
FD
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.
Bischoff
R
R
Fort
E
E
Brennan
M J
MJ
Locht
C
C
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