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Science 30 May 1997:
Vol. 276. no. 5317, pp. 1420 - 1422
DOI: 10.1126/science.276.5317.1420
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Reports

Role of the Major Antigen of Mycobacterium tuberculosis in Cell Wall Biogenesis

John T. Belisle, * Varalakshmi D. Vissa, Todd Sievert, Kuni Takayama, Patrick J. Brennan, Gurdyal S. Besra

The dominant exported proteins and protective antigens of Mycobacterium tuberculosis are a triad of related gene products called the antigen 85 (Ag85) complex. Each has also been implicated in disease pathogenesis through its fibronectin-binding capacities. A carboxylesterase domain was found within the amino acid sequences of Ag85A, B, and C, and each protein acted as a mycolyltransferase involved in the final stages of mycobacterial cell wall assembly, as shown by direct enzyme assay and site-directed mutagenesis. Furthermore, the use of an antagonist (6-azido-6-deoxy-alpha ,alpha '-trehalose) of this activity demonstrates that these proteins are essential and potential targets for new antimycobacterial drugs.

J. T. Belisle, V. D. Vissa, P. J. Brennan, G. S. Besra, Department of Microbiology, Colorado State University, Fort Collins, CO 80523, USA.
T. Sievert and K. Takayama, Mycobacteriology Research Laboratory, William S. Middleton Memorial Veterans Hospital, University of Wisconsin, Madison, WI 53705, USA.
*   To whom correspondence should be addressed. E-mail: jbelisle{at}vines.colostate.edu

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Microbiology 146, 199-208
   Abstract »    Full Text »
Conditional Sigma Factor Expression, Using the Inducible Acetamidase Promoter, Reveals that the Mycobacterium tuberculosis sigF Gene Modulates Expression of the 16-Kilodalton Alpha-Crystallin Homologue.
Y. C. Manabe, J. M. Chen, C. G. Ko, P. Chen, and W. R. Bishai (1999)
J. Bacteriol. 181, 7629-7633
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The PE-PGRS glycine-rich proteins of Mycobacterium tuberculosis : a new family of fibronectin-binding proteins?.
C. Espitia, J. P. Laclette, M. Mondragon- Palomino, A. Amador, J. Campuzano, A. Martens, M. Singh, R. Cicero, Y. Zhang, and C. Moreno (1999)
Microbiology 145, 3487-3495
   Abstract »    Full Text »    PDF »
Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization.
M. Wilson, J. DeRisi, H.-H. Kristensen, P. Imboden, S. Rane, P. O. Brown, and G. K. Schoolnik (1999)
PNAS 96, 12833-12838
   Abstract »    Full Text »    PDF »
Measurement of Sputum Mycobacterium tuberculosis Messenger RNA as a Surrogate for Response to Chemotherapy.
L. E. DESJARDIN, M. D. PERKINS, K. WOLSKI, S. HAUN, L. TEIXEIRA, Y. CHEN, J. L. JOHNSON, J. J. ELLNER, R. DIETZE, J. BATES, et al. (1999)
Am. J. Respir. Crit. Care Med. 160, 203-210
   Abstract »    Full Text »
T-Cell Epitope Mapping of the Three Most Abundant Extracellular Proteins of Mycobacterium tuberculosis in Outbred Guinea Pigs.
B.-Y. Lee and M. A. Horwitz (1999)
Infect. Immun. 67, 2665-2670
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Export of Recombinant Mycobacterium tuberculosis Superoxide Dismutase Is Dependent upon Both Information in the Protein and Mycobacterial Export Machinery. A MODEL FOR STUDYING EXPORT OF LEADERLESS PROTEINS BY PATHOGENIC MYCOBACTERIA.
G. Harth and M. A. Horwitz (1999)
J. Biol. Chem. 274, 4281-4292
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Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G.
S. I. Bentley-Hibbert, X. Quan, T. Newman, K. Huygen, and H. P. Godfrey (1999)
Infect. Immun. 67, 581-588
   Abstract »    Full Text »    PDF »
Definition of Natural T Cell Antigens with Mimicry Epitopes Obtained from Dedicated Synthetic Peptide Libraries.
H. S. Hiemstra, P. A. van Veelen, N. C. Schloot, A. Geluk, K. E. van Meijgaarden, S. J. M. Willemen, J. A. M. Leunissen, W. E. Benckhuijsen, R. Amons, R. R. P. de Vries, et al. (1998)
J. Immunol. 161, 4078-4082
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Mapping and Identification of the Major Cell Wall-Associated Components of Mycobacterium leprae.
M. A. M. Marques, S. Chitale, P. J. Brennan, and M. C. V. Pessolani (1998)
Infect. Immun. 66, 2625-2631
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Evaluation of New Vaccines in the Mouse and Guinea Pig Model of Tuberculosis.
S. L. Baldwin, C. D'Souza, A. D. Roberts, B. P. Kelly, A. A. Frank, M. A. Lui, J. B. Ulmer, K. Huygen, D. M. McMurray, and I. M. Orme (1998)
Infect. Immun. 66, 2951-2959
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Vaccination with Plasmid DNA Encoding Mycobacterial Antigen 85A Stimulates a CD4+ and CD8+ T-Cell Epitopic Repertoire Broader than That Stimulated by Mycobacterium tuberculosis H37Rv Infection.
O. Denis, A. Tanghe, K. Palfliet, F. Jurion, T.-P. van den Berg, A. Vanonckelen, J. Ooms, E. Saman, J. B. Ulmer, J. Content, et al. (1998)
Infect. Immun. 66, 1527-1533
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The Novel Fibronectin-binding Motif and Key Residues of Mycobacteria.
M. Naito, N. Ohara, S. Matsumoto, and T. Yamada (1998)
J. Biol. Chem. 273, 2905-2909
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Galactan Biosynthesis in Mycobacterium tuberculosis. IDENTIFICATION OF A BIFUNCTIONAL UDP-GALACTOFURANOSYLTRANSFERASE.
L. Kremer, L. G. Dover, C. Morehouse, P. Hitchin, M. Everett, H. R. Morris, A. Dell, P. J. Brennan, M. R. McNeil, C. Flaherty, et al. (2001)
J. Biol. Chem. 276, 26430-26440
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Recombinant bacillus Calmette-Guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model.
M. A. Horwitz, G. Harth, B. J. Dillon, and S. Maslesa-Galic' (2000)
PNAS 97, 13853-13858
   Abstract »    Full Text »    PDF »


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