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Journal of Bacteriology, December 1999, p. 7464-7469, Vol. 181, No. 24
0021-9193/99/$04.00+0
Functional Domains Present in the Mycobacterial
Hemagglutinin, HBHA
Giovanni
Delogu and
Michael J.
Brennan*
Center for Biologics Evaluation and Research,
Food and Drug Administration, Bethesda, Maryland 20892
Received 21 June 1999/Accepted 24 September 1999
Identification and characterization of mycobacterial adhesins and
complementary host receptors required for colonization and dissemination of mycobacteria in host tissues are needed for a more
complete understanding of the pathogenesis of diseases caused by these
bacteria and for the development of effective vaccines. Previous
investigations have demonstrated that a 28-kDa heparin-binding mycobacterial surface protein, HBHA, can agglutinate erythrocytes and
promote mycobacterial aggregation in vitro. In this study, further
molecular and biochemical analysis of HBHA demonstrates that it has
three functional domains: a transmembrane domain of 18 amino acids
residing near the N terminus, a large domain of 81 amino acids
consistent with an
-helical coiled-coil region, and a
Lys-Pro-Ala-rich C-terminal domain that mediates binding to
proteoglycans. Using His-tagged recombinant HBHA proteins and nickel
chromatography we demonstrate that HBHA polypeptides which contain the
coiled-coil region form multimers. This tendency to oligomerize may be
responsible for the induction of mycobacterial aggregation since a
truncated N-terminal HBHA fragment containing the coiled-coil domain
promotes mycobacterial aggregation. Conversely, a truncated C-terminal
HBHA fragment which contains Lys-Pro-Ala-rich repeats binds to the
proteoglycan decorin. These results indicate that HBHA contains at
least three distinct domains which facilitate intercalation into
surface membranes, promote bacterium-bacterium interactions, and
mediate the attachment to sulfated glycoconjugates found in host tissues.
*
Corresponding author. Mailing address: CBER/FDA, 29 Lincoln Dr. (HFM-431), Bethesda, MD 20892. Phone: (301) 496-9559. Fax: (301) 402-2776. E-mail: Brennan{at}cber.fda.gov.
Journal of Bacteriology, December 1999, p. 7464-7469, Vol. 181, No. 24
0021-9193/99/$04.00+0
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