Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

The Mycobacterial HBHA Protein: A Promising Biomarker for Tuberculosis

Author(s): Flavio De Maio, Flavia Squeglia, Delia Goletti and Giovanni Delogu*

Volume 26, Issue 11, 2019

Page: [2051 - 2060] Pages: 10

DOI: 10.2174/0929867325666181029165805

Price: $65


A major goal in tuberculosis (TB) research is the identification, among the subjects infected with Mycobacterium tuberculosis (Mtb), of those with active TB, or at higher risk of developing active disease, from the latently infected subjects. The classical heterogeneity of Mtb infection and TB disease is a major obstacle toward the identification of reliable biomarkers that can stratify Mtb infected subjects based on disease risk. The heparin-binding haemagglutinin (HBHA) is a mycobacterial surface antigen that is implicated in tuberculosis (TB) pathogenesis. The host immune response against HBHA varies depending on the TB status and several studies are supporting the role of HBHA as a useful biomarker of TB.

Keywords: Tuberculosis, biomarkers, HBHA, personalized medicine, Mycobacterium tuberculosis (Mtb), MDR-TB.

« Previous
World Health Organization. Global Tuberculosis Report 2018, 2018.
Dheda, K.; Gumbo, T.; Maartens, G.; Dooley, K.E.; McNerney, R.; Murray, M.; Furin, J.; Nardell, E.A.; London, L.; Lessem, E.; Theron, G.; van Helden, P.; Niemann, S.; Merker, M.; Dowdy, D.; Van Rie, A.; Siu, G.K.; Pasipanodya, J.G.; Rodrigues, C.; Clark, T.G.; Sirgel, F.A.; Esmail, A.; Lin, H.H.; Atre, S.R.; Schaaf, H.S.; Chang, K.C.; Lange, C.; Nahid, P.; Udwadia, Z.F.; Horsburgh, C.R., Jr; Churchyard, G.J.; Menzies, D.; Hesseling, A.C.; Nuermberger, E.; McIlleron, H.; Fennelly, K.P.; Goemaere, E.; Jaramillo, E.; Low, M.; Jara, C.M.; Padayatchi, N.; Warren, R.M. The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis. Lancet Respir. Med., 2017. S2213-2600(17)30079-6.
Delogu, G.; Goletti, D. The spectrum of tuberculosis infection: new perspectives in the era of biologics. J. Rheumatol. Suppl., 2014, 91, 11-16.
Houben, R.M.; Dodd, P.J. The global burden of latent tuberculosis infection: A Re-estimation using mathematical modelling. PLoS Med., 2016, 13(10)e1002152
Wolf, A.J.; Desvignes, L.; Linas, B.; Banaiee, N.; Tamura, T.; Takatsu, K.; Ernst, J.D. Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs. J. Exp. Med., 2008, 205(1), 105-115.
Gallegos, A.M.; Pamer, E.G.; Glickman, M.S. Delayed protection by ESAT-6-specific effector CD4+ T cells after airborne M. tuberculosis infection. J. Exp. Med., 2008, 205(10), 2359-2368.
Balasubramanian, V.; Wiegeshaus, E.H.; Taylor, B.T.; Smith, D.W. Pathogenesis of tuberculosis: Pathway to apical localization. Tuber. Lung Dis., 1994, 75(3), 168-178.
Hernández-Pando, R.; Jeyanathan, M.; Mengistu, G.; Aguilar, D.; Orozco, H.; Harboe, M.; Rook, G.A.; Bjune, G. Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet, 2000, 356(9248), 2133-2138.
Neyrolles, O.; Hernández-Pando, R.; Pietri-Rouxel, F.; Fornès, P.; Tailleux, L.; Barrios Payán, J.A.; Pivert, E.; Bordat, Y.; Aguilar, D.; Prévost, M.C.; Petit, C.; Gicquel, B. Is adipose tissue a place for Mycobacterium tuberculosis persistence? PLoS One, 2006, 1e43
Bishai, W.R. Rekindling old controversy on elusive lair of latent tuberculosis. Lancet, 2000, 356(9248), 2113-2114.
Pethe, K.; Alonso, S.; Biet, F.; Delogu, G.; Brennan, M.J.; Locht, C.; Menozzi, F.D. The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature, 2001, 412(6843), 190-194.
Cadena, A.M.; Flynn, J.L.; Fortune, S.M. The importance of first impressions: Early events in Mycobacterium tuberculosis infection influence outcome. MBio, 2016, 7(2), e00342-e16.
Lin, P.L.; Ford, C.B.; Coleman, M.T.; Myers, A.J.; Gawande, R.; Ioerger, T.; Sacchettini, J.; Fortune, S.M.; Flynn, J.L. Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing. Nat. Med., 2014, 20(1), 75-79.
Cadena, A.M.; Fortune, S.M.; Flynn, J.L. Heterogeneity in tuberculosis. Nat. Rev. Immunol., 2017, 17(11), 691-702.
Chao, M.C.; Rubin, E.J. Letting sleeping dos lie: Does dormancy play a role in tuberculosis? Annu. Rev. Microbiol., 2010, 64, 293-311.
Gengenbacher, M.; Kaufmann, S.H. Mycobacterium tuberculosis: Success through dormancy. FEMS Microbiol. Rev., 2012, 36(3), 514-532.
Pai, M. Spectrum of latent tuberculosis - existing tests cannot resolve the underlying phenotypes. Nat. Rev. Microbiol., 2010, 8(3), 242.
Goletti, D.; Sanduzzi, A.; Delogu, G. Performance of the tuberculin skin test and interferon-γ release assays: An update on the accuracy, cutoff stratification, and new potential immune-based approaches. J. Rheumatol. Suppl., 2014, 91, 24-31.
Petruccioli, E.; Scriba, T.J.; Petrone, L.; Hatherill, M.; Cirillo, D.M.; Joosten, S.A.; Ottenhoff, T.H.; Denkinger, C.M.; Goletti, D. Correlates of tuberculosis risk: Predictive biomarkers for progression to active tuberculosis. Eur. Respir. J., 2016, 48(6), 1751-1763.
Walzl, G.; Haks, M.C.; Joosten, S.A.; Kleynhans, L.; Ronacher, K.; Ottenhoff, T.H. Clinical immunology and multiplex biomarkers of human tuberculosis. Cold Spring Harb. Perspect. Med., 2014, 5(4)a018515
Lawn, S.D.; Kerkhoff, A.D.; Vogt, M.; Wood, R. Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: A descriptive study. Lancet Infect. Dis., 2012, 12(3), 201-209.
Pandie, S.; Peter, J.G.; Kerbelker, Z.S.; Meldau, R.; Theron, G.; Govender, U.; Ntsekhe, M.; Dheda, K.; Mayosi, B.M. The diagnostic accuracy of pericardial and urinary lipoarabinomannan (LAM) assays in patients with suspected tuberculous pericarditis. Sci. Rep., 2016, 6, 32924.
Hanifa, Y.; Telisinghe, L.; Fielding, K.L.; Malden, J.L.; Churchyard, G.J.; Grant, A.D.; Charalambous, S. The diagnostic accuracy of urine lipoarabinomannan test for tuberculosis screening in a South African correctional facility. PLoS One, 2015, 10(5)e0127956
Paris, L.; Magni, R.; Zaidi, F.; Araujo, R.; Saini, N.; Harpole, M.; Coronel, J.; Kirwan, D.E.; Steinberg, H.; Gilman, R.H.; Petricoin, E.F., III; Nisini, R.; Luchini, A.; Liotta, L. Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity. Sci. Transl. Med., 2017, 9(420)eaal2807
Berry, M.P.; Graham, C.M.; McNab, F.W.; Xu, Z.; Bloch, S.A.; Oni, T.; Wilkinson, K.A.; Banchereau, R.; Skinner, J.; Wilkinson, R.J.; Quinn, C.; Blankenship, D.; Dhawan, R.; Cush, J.J.; Mejias, A.; Ramilo, O.; Kon, O.M.; Pascual, V.; Banchereau, J.; Chaussabel, D.; O’Garra, A. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature, 2010, 466(7309), 973-977.
Zak, D.E.; Penn-Nicholson, A.; Scriba, T.J.; Thompson, E.; Suliman, S.; Amon, L.M.; Mahomed, H.; Erasmus, M.; Whatney, W.; Hussey, G.D.; Abrahams, D.; Kafaar, F.; Hawkridge, T.; Verver, S.; Hughes, E.J.; Ota, M.; Sutherland, J.; Howe, R.; Dockrell, H.M.; Boom, W.H.; Thiel, B.; Ottenhoff, T.H.M.; Mayanja-Kizza, H.; Crampin, A.C.; Downing, K.; Hatherill, M.; Valvo, J.; Shankar, S.; Parida, S.K.; Kaufmann, S.H.E.; Walzl, G.; Aderem, A.; Hanekom, W.A. A blood RNA signature for tuberculosis disease risk: a prospective cohort study. Lancet, 2016, 387(10035), 2312-2322.
Maertzdorf, J.; McEwen, G.; Weiner, J., III; Tian, S.; Lader, E.; Schriek, U.; Mayanja-Kizza, H.; Ota, M.; Kenneth, J.; Kaufmann, S.H. Concise gene signature for point-of-care classification of tuberculosis. EMBO Mol. Med., 2016, 8(2), 86-95.
Duffy, F.J.; Thompson, E.; Downing, K.; Suliman, S.; Mayanja-Kizza, H.; Boom, W.H.; Thiel, B.; Weiner Iii, J.; Kaufmann, S.H.E.; Dover, D.; Tabb, D.L.; Dockrell, H.M.; Ottenhoff, T.H.M.; Tromp, G.; Scriba, T.J.; Zak, D.E.; Walzl, G. A serum circulating miRNA signature for short-term risk of progression to active tuberculosis among household contacts. Front. Immunol., 2018, 9, 661.
Singhania, A.; Verma, R.; Graham, C.M.; Lee, J.; Tran, T.; Richardson, M.; Lecine, P.; Leissner, P.; Berry, M.P.R.; Wilkinson, R.J.; Kaiser, K.; Rodrigue, M.; Woltmann, G.; Haldar, P.; O’Garra, A. A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection. Nat. Commun., 2018, 9(1), 2308.
Suliman, S.; Thompson, E.; Sutherland, J.; Weiner Rd, J.; Ota, M.O.C.; Shankar, S.; Penn-Nicholson, A.; Thiel, B.; Erasmus, M.; Maertzdorf, J.; Duffy, F.J.; Hill, P.C.; Hughes, E.J.; Stanley, K.; Downing, K.; Fisher, M.L.; Valvo, J.; Parida, S.K.; van der Spuy, G.; Tromp, G.; Adetifa, I.M.O.; Donkor, S.; Howe, R.; Mayanja-Kizza, H.; Boom, W.H.; Dockrell, H.; Ottenhoff, T.H.M.; Hatherill, M.; Aderem, A.; Hanekom, W.A.; Scriba, T.J.; Kaufmann, S.H.; Zak, D.E.; Walzl, G. Four-gene pan-african blood signature predicts progression to tuberculosis. Am. J. Respir. Crit. Care Med., 2018.
Steingart, K.R.; Flores, L.L.; Dendukuri, N.; Schiller, I.; Laal, S.; Ramsay, A.; Hopewell, P.C.; Pai, M. Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: an updated systematic review and meta-analysis. PLoS Med., 2011, 8(8)e1001062
Dowdy, D.W.; Steingart, K.R.; Pai, M. Serological testing versus other strategies for diagnosis of active tuberculosis in India: A cost-effectiveness analysis. PLoS Med., 2011, 8(8)e1001074
Ling, D.I.; Pai, M.; Davids, V.; Brunet, L.; Lenders, L.; Meldau, R.; Calligaro, G.; Allwood, B.; van Zyl-Smit, R.; Peter, J.; Bateman, E.; Dawson, R.; Dheda, K. Are interferon-γ release assays useful for diagnosing active tuberculosis in a high-burden setting? Eur. Respir. J., 2011, 38(3), 649-656.
Baird, M.S. New synthetic lipid antigens for rapid serological diagnosis of tuberculosis. PLoS One, 2017, Aug 14;. 12(8)e0181414
Legesse, M.; Ameni, G.; Medhin, G.; Mamo, G.; Franken, K.L.; Ottenhoff, T.H.; Bjune, G.; Abebe, F. IgA response to ESAT-6/CFP-10 and Rv2031 antigens varies in patients with culture-confirmed pulmonary tuberculosis, healthy Mycobacterium tuberculosis-infected and non-infected individuals in a tuberculosis endemic setting, Ethiopia. Scand. J. Immunol., 2013, 78(3), 266-274.
Zimmermann, N.; Thormann, V.; Hu, B.; Köhler, A.B.; Imai-Matsushima, A.; Locht, C.; Arnett, E.; Schlesinger, L.S.; Zoller, T.; Schürmann, M.; Kaufmann, S.H.; Wardemann, H. Human isotype-dependent inhibitory antibody responses against Mycobacterium tuberculosis. EMBO Mol. Med., 2016, 8(11), 1325-1339.
Lu, L.L.; Chung, A.W.; Rosebrock, T.R.; Ghebremichael, M.; Yu, W.H.; Grace, P.S.; Schoen, M.K.; Tafesse, F.; Martin, C.; Leung, V.; Mahan, A.E.; Sips, M.; Kumar, M.P.; Tedesco, J.; Robinson, H.; Tkachenko, E.; Draghi, M.; Freedberg, K.J.; Streeck, H.; Suscovich, T.J.; Lauffenburger, D.A.; Restrepo, B.I.; Day, C.; Fortune, S.M.; Alter, G. A functional role for antibodies in tuberculosis. Cell, 2016, 167(2), 433-443.e14.
Casadevall, A. Antibodies to Mycobacterium tuberculosis. N. Engl. J. Med., 2017, 376(3), 283-285.
Pai, M.; Joshi, R.; Dogra, S.; Zwerling, A.A.; Gajalakshmi, D.; Goswami, K.; Reddy, M.V.; Kalantri, A.; Hill, P.C.; Menzies, D.; Hopewell, P.C. T-cell assay conversions and reversions among household contacts of tuberculosis patients in rural India. Int. J. Tuberc. Lung Dis., 2009, 13(1), 84-92.
Andersen, P.; Doherty, T.M.; Pai, M.; Weldingh, K. The prognosis of latent tuberculosis: Can disease be predicted? Trends Mol. Med., 2007, 13(5), 175-182.
Andrews, J.R.; Nemes, E.; Tameris, M.; Landry, B.S.; Mahomed, H.; McClain, J.B.; Fletcher, H.A.; Hanekom, W.A.; Wood, R.; McShane, H.; Scriba, T.J.; Hatherill, M. Serial QuantiFERON testing and tuberculosis disease risk among young children: An observational cohort study. Lancet Respir. Med., 2017, 5(4), 282-290.
Vanini, V.; Petruccioli, E.; Gioia, C.; Cuzzi, G.; Orchi, N.; Rianda, A.; Alba, L.; Giancola, M.L.; Conte, A.; Schininà, V.; Rizzi, E.B.; Girardi, E.; Goletti, D. IP-10 is an additional marker for tuberculosis (TB) detection in HIV-infected persons in a low-TB endemic country. J. Infect., 2012, 65(1), 49-59.
Cirillo, D.M.; Barcellini, L.; Goletti, D. Preliminary data on precision of QuantiFERON-TB Plus performance. Eur. Respir. J., 2016, 48(3), 955-956.
Petruccioli, E.; Chiacchio, T.; Pepponi, I.; Vanini, V.; Urso, R.; Cuzzi, G.; Barcellini, L.; Cirillo, D.M.; Palmieri, F.; Ippolito, G.; Goletti, D. First characterization of the CD4 and CD8 T-cell responses to QuantiFERON-TB Plus. J. Infect., 2016, 73(6), 588-597.
Delogu, G.; Brennan, M.J. Functional domains present in the mycobacterial hemagglutinin, HBHA. J. Bacteriol., 1999, 181(24), 7464-7469.
Esposito, C.; Pethoukov, M.V.; Svergun, D.I.; Ruggiero, A.; Pedone, C.; Pedone, E.; Berisio, R. Evidence for an elongated dimeric structure of heparin-binding hemagglutinin from Mycobacterium tuberculosis. J. Bacteriol., 2008, 190(13), 4749-4753.
Delogu, G.; Fadda, G.; Brennan, M.J. Impact of structural domains of the heparin binding hemagglutinin of Mycobacterium tuberculosis on function. Protein Pept. Lett., 2012, 19(10), 1035-1039.
van der Wel, N.; Hava, D.; Houben, D.; Fluitsma, D.; van Zon, M.; Pierson, J.; Brenner, M.; Peters, P.J.M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell, 2007, 129(7), 1287-1298.
Pethe, K.; Bifani, P.; Drobecq, H.; Sergheraert, C.; Debrie, A.S.; Locht, C.; Menozzi, F.D. Mycobacterial heparin-binding hemagglutinin and laminin-binding protein share antigenic methyllysines that confer resistance to proteolysis. Proc. Natl. Acad. Sci. USA, 2002, 99(16), 10759-10764.
Temmerman, S.; Pethe, K.; Parra, M.; Alonso, S.; Rouanet, C.; Pickett, T.; Drowart, A.; Debrie, A.S.; Delogu, G.; Menozzi, F.D.; Sergheraert, C.; Brennan, M.J.; Mascart, F.; Locht, C. Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin. Nat. Med., 2004, 10(9), 935-941.
Dupres, V.; Menozzi, F.D.; Locht, C.; Clare, B.H.; Abbott, N.L.; Cuenot, S.; Bompard, C.; Raze, D.; Dufrêne, Y.F. Nanoscale mapping and functional analysis of individual adhesins on living bacteria. Nat. Methods, 2005, 2(7), 515-520.
Verbelen, C.; Raze, D.; Dewitte, F.; Locht, C.; Dufrêne, Y.F. Single-molecule force spectroscopy of mycobacterial adhesin-adhesin interactions. J. Bacteriol., 2007, 189(24), 8801-8806.
Menozzi, F.D.; Rouse, J.H.; Alavi, M.; Laude-Sharp, M.; Muller, J.; Bischoff, R.; Brennan, M.J.; Locht, C. Identification of a heparin-binding hemagglutinin present in mycobacteria. J. Exp. Med., 1996, 184(3), 993-1001.
Delogu, G.; Sanguinetti, M.; Posteraro, B.; Rocca, S.; Zanetti, S.; Fadda, G. The hbhA gene of Mycobacterium Tuberculosis is specifically upregulated in the lungs but not in the spleens of aerogenically infected mice. Infect. Immun., 2006, 74(5), 3006-3011.
Menozzi, F.D.; Reddy, V.M.; Cayet, D.; Raze, D.; Debrie, A.S.; Dehouck, M.P. Mycobacterium tuberculosis heparin-binding haemagglutinin adhesin (HBHA) triggers receptor-mediated transcytosis without althering the integrity of tight junctions. Microbes Infect., 2005, 8(1), 1-9.
Lebrun, P.; Raze, D.; Fritzinger, B.; Wieruszeski, J.M.; Biet, F.; Dose, A.; Carpentier, M.; Schwarzer, D.; Allain, F.; Lippens, G.; Locht, C. Differential contribution of the repeats to heparin binding of HBHA, a major adhesin of Mycobacterium tuberculosis. PLoS One, 2012, 7(3)e32421
Esposito, C.; Marasco, D.; Delogu, G.; Pedone, E.; Berisio, R. Heparin-binding hemagglutinin HBHA from Mycobacterium Tuberculosis affects actin polymerisation. Biochem. Biophys. Res. Commun., 2011, 410(2), 339-344.
Verbelen, C.; Dupres, V.; Raze, D.; Bompard, C.; Locht, C.; Dufrêne, Y.F. Interaction of the mycobacterial heparin-binding hemagglutinin with actin, as evidenced by single-molecule force spectroscopy. J. Bacteriol., 2008, 190(23), 7614-7620.
Lanfranconi, M.P.; Alvarez, H.M. Functional divergence of HBHA from Mycobacterium Tuberculosis and its evolutionary relationship with TadA from Rhodococcus opacus. Biochimie, 2016, 127, 241-248.
Biet, F.; Angela de Melo Marques, M.; Grayon, M.; Xavier da Silveira, E.K.; Brennan, P.J.; Drobecq, H.; Raze, D.; Vidal Pessolani, M.C.; Locht, C.; Menozzi, F.D. Mycobacterium smegmatis produces an HBHA homologue which is not involved in epithelial adherence. Microbes Infect., 2007, 9(2), 175-182.
Esposito, C.; Carullo, P.; Pedone, E.; Graziano, G.; Del Vecchio, P.; Berisio, R. Dimerisation and structural integrity of Heparin Binding Hemagglutinin A from Mycobacterium Tuberculosis: implications for bacterial agglutination. FEBS Lett., 2010, 584(6), 1091-1096.
Menozzi, F.D.; Reddy, V.M.; Cayet, D.; Raze, D.; Debrie, A.S.; Dehouck, M.P.; Cecchelli, R.; Locht, C. Mycobacterium tuberculosis heparin-binding haemagglutinin adhesin (HBHA) triggers receptor-mediated transcytosis without altering the integrity of tight junctions. Microbes Infect., 2006, 8(1), 1-9.
Menozzi, F.D.; Bischoff, R.; Fort, E.; Brennan, M.J.; Locht, C. Molecular characterization of the mycobacterial heparin-binding hemagglutinin, a mycobacterial adhesin. Proc. Natl. Acad. Sci. USA, 1998, 95(21), 12625-12630.
Esposito, C.; Cantisani, M.; D’Auria, G.; Falcigno, L.; Pedone, E.; Galdiero, S.; Berisio, R. Mapping key interactions in the dimerization process of HBHA from Mycobacterium tuberculosis, insights into bacterial agglutination. FEBS Lett., 2012, 586(6), 659-667.
Huang, T.Y.; Irene, D.; Zulueta, M.M.; Tai, T.J.; Lain, S.H.; Cheng, C.P.; Tsai, P.X.; Lin, S.Y.; Chen, Z.G.; Ku, C.C.; Hsiao, C.D.; Chyan, C.L.; Hung, S.C. Structure of the complex between a heparan sulfate octasaccharide and mycobacterial heparin-binding hemagglutinin. Angew. Chem. Int. Ed. Engl., 2017, 56(15), 4192-4196.
Masungi, C.; Temmerman, S.; Van Vooren, J.P.; Drowart, A.; Pethe, K.; Menozzi, F.D.; Locht, C.; Mascart, F. Differential T and B cell responses against Mycobacterium tuberculosis heparin-binding hemagglutinin adhesin in infected healthy individuals and patients with tuberculosis. J. Infect. Dis., 2002, 185(4), 513-520.
Zanetti, S.; Bua, A.; Delogu, G.; Pusceddu, C.; Mura, M.; Saba, F.; Pirina, P.; Garzelli, C.; Vertuccio, C.; Sechi, L.A.; Fadda, G. Patients with pulmonary tuberculosis develop a strong humoral response against methylated heparin-binding hemagglutinin. Clin. Diagn. Lab. Immunol., 2005, 12(9), 1135-1138.
Belay, M.; Legesse, M.; Mihret, A.; Ottenhoff, T.H.; Franken, K.L.; Bjune, G.; Abebe, F. IFN-γ and IgA against non-methylated heparin-binding hemagglutinin as markers of protective immunity and latent tuberculosis: Results of a longitudinal study from an endemic setting. J. Infect., 2016, 72(2), 189-200.
Delogu, G.; Bua, A.; Pusceddu, C.; Parra, M.; Fadda, G.; Brennan, M.J.; Zanetti, S. Expression and purification of recombinant methylated HBHA in Mycobacterium smegmatis. FEMS Microbiol. Lett., 2004, 239(1), 33-39.
Delogu, G.; Chiacchio, T.; Vanini, V.; Butera, O.; Cuzzi, G.; Bua, A.; Molicotti, P.; Zanetti, S.; Lauria, F.N.; Grisetti, S.; Magnavita, N.; Fadda, G.; Girardi, E.; Goletti, D. Methylated HBHA produced in M. smegmatis discriminates between active and non-active tuberculosis disease among RD1-responders. PLoS One, 2011, 6(3)e18315
Corbière, V.; Pottier, G.; Bonkain, F.; Schepers, K.; Verscheure, V.; Lecher, S.; Doherty, T.M.; Locht, C.; Mascart, F. Risk stratification of latent tuberculosis defined by combined interferon gamma release assays. PLoS One, 2012, 7(8)e43285
Delogu, G.; Vanini, V.; Cuzzi, G.; Chiacchio, T.; De Maio, F.; Battah, B.; Pinnetti, C.; Sampaolesi, A.; Antinori, A.; Goletti, D. Lack of response to HBHA in HIV-infected patients with latent tuberculosis infection. Scand. J. Immunol., 2016, 84(6), 344-352.
Chiacchio, T.; Delogu, G.; Vanini, V.; Cuzzi, G.; De Maio, F.; Pinnetti, C.; Sampaolesi, A.; Antinori, A.; Goletti, D. Immune characterization of the HBHA-specific response in Mycobacterium tuberculosis-infected patients with or without HIV infection. PLoS One, 2017, 12(8)e0183846
Wen, H.L.; Li, C.L.; Li, G.; Lu, Y.H.; Li, H.C.; Li, T.; Zhao, H.M.; Wu, K.; Lowrie, D.B.; Lv, J.X.; Lu, S.H.; Fan, X.Y. Involvement of methylated HBHA expressed from Mycobacterium smegmatis in an IFN-γ release assay to aid discrimination between latent infection and active tuberculosis in BCG-vaccinated populations. Eur. J. Clin. Microbiol. Infect. Dis., 2017, 36(8), 1415-1423.
Hougardy, J.M.; Place, S.; Hildebrand, M.; Drowart, A.; Debrie, A.S.; Locht, C.; Mascart, F. Regulatory T cells depress immune responses to protective antigens in active tuberculosis. Am. J. Respir. Crit. Care Med., 2007, 176(4), 409-416.
Boer, M.C.; van Meijgaarden, K.E.; Goletti, D.; Vanini, V.; Prins, C.; Ottenhoff, T.H.; Joosten, S.A. KLRG1 and PD-1 expression are increased on T-cells following tuberculosis-treatment and identify cells with different proliferative capacities in BCG-vaccinated adults. Tuberculosis (Edinb.), 2016, 97, 163-171.
Parra, M.; Pickett, T.; Delogu, G.; Dheenadhayalan, V.; Debrie, A.S.; Locht, C.; Brennan, M.J. The mycobacterial heparin-binding hemagglutinin is a protective antigen in the mouse aerosol challenge model of tuberculosis. Infect. Immun., 2004, 72(12), 6799-6805.
Delogu, G.; Fadda, G. The quest for a new vaccine against tuberculosis. J. Infect. Dev. Ctries., 2009, 3(1), 5-15.
Smith, S.G.; Lecher, S.; Blitz, R.; Locht, C.; Dockrell, H.M. Broad heparin-binding haemagglutinin-specific cytokine and chemokine response in infants following Mycobacterium bovis BCG vaccination. Eur. J. Immunol., 2012, 42(9), 2511-2522.
Rouanet, C.; Debrie, A.S.; Lecher, S.; Locht, C. Subcutaneous boosting with heparin binding haemagglutinin increases BCG-induced protection against tuberculosis. Microbes Infect., 2009, 11(13), 995-1001.
Guerrero, G.G.; Debrie, A.S.; Locht, C. Boosting with mycobacterial heparin-binding haemagglutinin enhances protection of Mycobacterium bovis BCG-vaccinated newborn mice against M. tuberculosis. Vaccine, 2010, 28(27), 4340-4347.
Verwaerde, C.; Debrie, A.S.; Dombu, C.; Legrand, D.; Raze, D.; Lecher, S.; Betbeder, D.; Locht, C. HBHA vaccination may require both Th1 and Th17 immune responses to protect mice against tuberculosis. Vaccine, 2014, 32(47), 6240-6250.
Kohama, H.; Umemura, M.; Okamoto, Y.; Yahagi, A.; Goga, H.; Harakuni, T.; Matsuzaki, G.; Arakawa, T. Mucosal immunization with recombinant heparin-binding haemagglutinin adhesin suppresses extrapulmonary dissemination of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in infected mice. Vaccine, 2008, 26(7), 924-932.
Fukui, M.; Shinjo, K.; Umemura, M.; Shigeno, S.; Harakuni, T.; Arakawa, T.; Matsuzaki, G. Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen. Microbiol. Immunol., 2015, 59(12), 735-743.
Stylianou, E.; Diogo, G.R.; Pepponi, I.; van Dolleweerd, C.; Arias, M.A.; Locht, C.; Rider, C.C.; Sibley, L.; Cutting, S.M.; Loxley, A.; Ma, J.K.; Reljic, R. Mucosal delivery of antigen-coated nanoparticles to lungs confers protective immunity against tuberculosis infection in mice. Eur. J. Immunol., 2014, 44(2), 440-449.
Hart, P.; Copland, A.; Diogo, G.R.; Harris, S.; Spallek, R.; Oehlmann, W.; Singh, M.; Basile, J.; Rottenberg, M.; Paul, M.J.; Reljic, R. Nanoparticle-fusion protein complexes protect against Mycobacterium tuberculosis infection. Mol. Ther., 2018, 26(3), 822-833.
Copland, A.; Diogo, G.R.; Hart, P.; Harris, S.; Tran, A.C.; Paul, M.J.; Singh, M.; Cutting, S.M.; Reljic, R. Mucosal delivery of fusion proteins with Bacillus subtilis spores enhances protection against tuberculosis by bacillus calmette-guérin. Front. Immunol., 2018, 9, 346.
Esposito, C.; Carullo, P.; Pedone, E.; Graziano, G.; Del Vecchio, P.; Berisio, R. Dimerisation and structural integrity of heparin binding Hemagglutinin A from Mycobacterium tuberculosis: Implications for bacterial agglutination. FEBS Lett., 2010, 584(6), 1091-1096.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy