19 The Mycobacterial Heparin-Binding Hemagglutinin: a Virulence Factor and Antigen Useful for Diagnostics and Vaccine Development

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One of the most recently characterized mycobacterial cell wall proteins is the heparin-binding hemagglutinin (HBHA). Initially found on the surface of and bacillus Calmette-Guérin (BCG), HBHA is also present on the surface of other mycobacteria, including other pathogenic and nonpathogenic species. The direct role of HBHA in bacterial adherence to epithelial cells was confirmed by the use of isogenic mutant strains. When the mutation is complemented by the natural gene under the control of its own promoter, binding to the A549 cells is restored to wild-type levels. These observations confirm that HBHA is one of the key adhesins for cells other than professional phagocytes, suggesting that interactions of with cells other than macrophages may play an important role in the pathogenesis of tuberculosis. Purified HBHA also binds to concanavalin A, which was initially proposed to indicate that HBHA may be a glycoprotein. The fact that HBHA is surface exposed despite the lack of a cleavable N-terminal signal peptide suggests that its cellular localization is Sec independent. The localization of HBHA at the mycobacterial membrane may be mediated by the putative hydrophobic N-proximal transmembrane domain. Cytotoxicity appeared to be independent of host factors and was thus proposed to be driven by bacterial virulence factors.

Citation: Locht C, Raze D, Rouanet C, Genisset C, Segers J, Mascart F. 2008. 19 The Mycobacterial Heparin-Binding Hemagglutinin: a Virulence Factor and Antigen Useful for Diagnostics and Vaccine Development, p 305-321. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch19
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Image of Figure 1.
Figure 1.

Predicted secondary structure of HBHA. (A) The secondary structure of HBHA was predicted by using PROF (University of Wales, Aberystwyth Computational Biology Group). Predicted alpha helices are depicted as cylinders below the amino acid sequence, L represents predicted loop structures, and * represents unpredicted structures due to low reliability of structure prediction. The open box represents the hydrophobic region, and the gray box represents the predicted coiled-coil region. (B) Coiled-coil propensity. The probability that the protein will adopt a coiled-coil conformation was calculated by the Coils server (ch.EMBnet.org) and was obtained by using default options in scanning windows of 14, 21, and 28 residues, as indicated.

Citation: Locht C, Raze D, Rouanet C, Genisset C, Segers J, Mascart F. 2008. 19 The Mycobacterial Heparin-Binding Hemagglutinin: a Virulence Factor and Antigen Useful for Diagnostics and Vaccine Development, p 305-321. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch19
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Image of Figure 2.
Figure 2.

Structure of the locus in different bacterial species. The gene of the different species indicated is highlighted as the arrow in bold. Conserved open reading frames between the different species are shown by the same color. The corresponding putative proteins encoded by the genes are indicated on the top. Chromosomal deletions or absence of genes are indicated by the dotted lines, and pseudogenes in are depicted by the crosses.

Citation: Locht C, Raze D, Rouanet C, Genisset C, Segers J, Mascart F. 2008. 19 The Mycobacterial Heparin-Binding Hemagglutinin: a Virulence Factor and Antigen Useful for Diagnostics and Vaccine Development, p 305-321. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch19
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Image of Figure 3.
Figure 3.

Alignments of the HBHA sequences form different mycobacterial (A) and nonmycobacterial (B) species. Strictly conserved residues are boxed in black, similar residues are boxed in gray, and dashes indicate gaps. Mtb H37Rv, H37Rv; Mbo, ; Mbo BCG, BCG; Mma, ; Maf, ; Mul, ; Mmi, ; Mav, M. ; Map, subsp. ; Mle, ; Msm, ; Mfl, ; Mva, ; . JLS, strain JLS; . KMS, strain KMS; RHA1, strain RHA1; 10152, ; SK2, .

Citation: Locht C, Raze D, Rouanet C, Genisset C, Segers J, Mascart F. 2008. 19 The Mycobacterial Heparin-Binding Hemagglutinin: a Virulence Factor and Antigen Useful for Diagnostics and Vaccine Development, p 305-321. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch19
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