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Microbiology 144 (1998), 3195-3203; DOI  10.1099/00221287-144-11-3195
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A Mycobacterium tuberculosis operon encoding ESAT=6 and a novel low-molecular-mass culture filtrate protein (CFP-10)

Fransois-Xavier Berthet1,{dagger},3, Peter Birk Rasmussen2, Ida Rosenkrands2, Peter Andersen2 and Brigitte Gicquel1

Unite de Genetique MycobactCrienne, lnstitut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France
Department of Tuberculosis Immunology, Statens Seruminstitut, 5 Artilleri vej, DK 2300 Copenhagen S Denmark

3Author for correspondence: Fransois-Xavier Berthet. Tel: +32 2 656 85 93. Fax: +32 2 656 81 13.e-mail: berthet@sbbio.be

ABSTRACT

SUMMARY: The early secreted antigenic target 6 kDa protein (ESAT-6) is a potent T-cell protein antigen synthesized by Mycobacterium tuberculosis. Its corresponding gene (esat-6) is located in RD1, a 10 kb DNA region deleted in the attenuated tuberculosis vaccine strain Mycobacterium bowis BCG. The promoter region of M. tuberculosis esat-6 was cloned and characterized. A new gene, designated lhp and cotranscribed with esat-6, was identified. Moreover, computer searches in the M. tuberculosis genome identified 13 genes related to the lhplesat-6 operon, defining a novel gene family. The transcription initiation sites of the lhplesat-6 operon were mapped using M. tuberculosis RNA. The corresponding promoter signals were not recognized in Mycobacterium smegmatis, in whichtranscription of lhplesat-6 is initiated at different locations. The M. tuberculosis lhp gene product was identified as CFP-10, a low- molecular-mass protein found in the short-term culture filtrate. These results show that the genes encoding CFP-10 and ESAT-6 are transcribed together in M. tuberculosis and that both code for small exported proteins.

Keywords: tuberculosis, Mycobacterium tuberculosis, operon, ESAT-6, CFP-10

{dagger} Present address: Bacterial Antigen Discovery group, SmithKline Beecham Biologicals, Rue de L'institut, 89, B-1330 Rixensart, Belgium




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D. C. Flyer, V. Ramakrishna, C. Miller, H. Myers, M. McDaniel, K. Root, C. Flournoy, V. H. Engelhard, D. H. Canaday, J. A. Marto, et al.
Identification by Mass Spectrometry of CD8+-T-Cell Mycobacterium tuberculosis Epitopes within the Rv0341 Gene Product
Infect. Immun., June 1, 2002; 70(6): 2926 - 2932.
[Abstract] [Full Text] [PDF]

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A. Geluk, K. E. van Meijgaarden, K. L. M. C. Franken, Y. W. Subronto, B. Wieles, S. M. Arend, E. P. Sampaio, T. de Boer, W. R. Faber, B. Naafs, et al.
Identification and Characterization of the ESAT-6 Homologue of Mycobacterium leprae and T-Cell Cross-Reactivity with Mycobacterium tuberculosis
Infect. Immun., May 1, 2002; 70(5): 2544 - 2548.
[Abstract] [Full Text] [PDF]

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 J. Clin. Microbiol.Home page
T. M. Doherty, A. Demissie, J. Olobo, D. Wolday, S. Britton, T. Eguale, P. Ravn, and P. Andersen
Immune Responses to the Mycobacterium tuberculosis-Specific Antigen ESAT-6 Signal Subclinical Infection among Contacts of Tuberculosis Patients
J. Clin. Microbiol., February 1, 2002; 40(2): 704 - 706.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
J. S. Spencer, M. A. M. Marques, M. C. B. S. Lima, A. P. Junqueira-Kipnis, B. C. Gregory, R. W. Truman, and P. J. Brennan
Antigenic Specificity of the Mycobacterium leprae Homologue of ESAT-6
Infect. Immun., February 1, 2002; 70(2): 1010 - 1013.
[Abstract] [Full Text] [PDF]

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 CVIHome page
S. M. Arend, A. C. F. Engelhard, G. Groot, K. de Boer, P. Andersen, T. H. M. Ottenhoff, and J. T. van Dissel
Tuberculin Skin Testing Compared with T-Cell Responses to Mycobacterium tuberculosis-Specific and Nonspecific Antigens for Detection of Latent Infection in Persons with Recent Tuberculosis Contact
Clin. Vaccine Immunol., November 1, 2001; 8(6): 1089 - 1096.
[Abstract] [Full Text] [PDF]

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 CVIHome page
H. M. Vordermeier, A. Whelan, P. J. Cockle, L. Farrant, N. Palmer, and R. G. Hewinson
Use of Synthetic Peptides Derived from the Antigens ESAT-6 and CFP-10 for Differential Diagnosis of Bovine Tuberculosis in Cattle
Clin. Vaccine Immunol., May 1, 2001; 8(3): 571 - 578.
[Abstract] [Full Text] [PDF]

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 J. Bacteriol.Home page
C. Le Dantec, N. Winter, B. Gicquel, V. Vincent, and M. Picardeau
Genomic Sequence and Transcriptional Analysis of a 23-Kilobase Mycobacterial Linear Plasmid: Evidence for Horizontal Transfer and Identification of Plasmid Maintenance Systems
J. Bacteriol., April 1, 2001; 183(7): 2157 - 2164.
[Abstract] [Full Text]

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 J. Immunol.Home page
D. M. Lewinsohn, L. Zhu, V. J. Madison, D. C. Dillon, S. P. Fling, S. G. Reed, K. H. Grabstein, and M. R. Alderson
Classically Restricted Human CD8+ T Lymphocytes Derived from Mycobacterium tuberculosis-Infected Cells: Definition of Antigenic Specificity
J. Immunol., January 1, 2001; 166(1): 439 - 446.
[Abstract] [Full Text] [PDF]

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 MicrobiologyHome page
J. C. Betts, P. Dodson, S. Quan, A. P. Lewis, P. J. Thomas, K. Duncan, and R. A. McAdam
Comparison of the proteome of Mycobacterium tuberculosis strain H37Rv with clinical isolate CDC 1551
Microbiology, December 1, 2000; 146(12): 3205 - 3216.
[Abstract] [Full Text] [PDF]

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 J. Clin. Microbiol.Home page
D. C. Dillon, M. R. Alderson, C. H. Day, T. Bement, A. Campos-Neto, Y. A. W. Skeiky, T. Vedvick, R. Badaro, S. G. Reed, and R. Houghton
Molecular and Immunological Characterization of Mycobacterium tuberculosis CFP-10, an Immunodiagnostic Antigen Missing in Mycobacterium bovis BCG
J. Clin. Microbiol., September 1, 2000; 38(9): 3285 - 3290.
[Abstract] [Full Text]

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 Infect. Immun.Home page
S. M. Arend, A. Geluk, K. E. van Meijgaarden, J. T. van Dissel, M. Theisen, P. Andersen, and T. H. M. Ottenhoff
Antigenic Equivalence of Human T-Cell Responses to Mycobacterium tuberculosis-Specific RD1-Encoded Protein Antigens ESAT-6 and Culture Filtrate Protein 10 and to Mixtures of Synthetic Peptides
Infect. Immun., June 1, 2000; 68(6): 3314 - 3321.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
J. M. Musser, A. Amin, and S. Ramaswamy
Negligible Genetic Diversity of Mycobacterium tuberculosis Host Immune System Protein Targets: Evidence of Limited Selective Pressure
Genetics, May 1, 2000; 155(1): 7 - 16.
[Abstract] [Full Text]

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 MicrobiologyHome page
F. Bigi, A. Alito, M. I. Romano, M. Zumarraga, K. Caimi, and A. Cataldi
The gene encoding P27 lipoprotein and a putative antibiotic-resistance gene form an operon in Mycobacterium tuberculosis and Mycobacterium bovis
Microbiology, April 1, 2000; 146(4): 1011 - 1018.
[Abstract] [Full Text]

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 CVIHome page
L. A. H. van Pinxteren, P. Ravn, E. M. Agger, J. Pollock, and P. Andersen
Diagnosis of Tuberculosis Based on the Two Specific Antigens ESAT-6 and CFP10
Clin. Vaccine Immunol., March 1, 2000; 7(2): 155 - 160.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
R. Colangeli, J. S. Spencer, P. Bifani, A. Williams, K. Lyashchenko, M. A. Keen, P. J. Hill, J. Belisle, and M. L. Gennaro
MTSA-10, the Product of the Rv3874 Gene of Mycobacterium tuberculosis, Elicits Tuberculosis-Specific, Delayed-Type Hypersensitivity in Guinea Pigs
Infect. Immun., February 1, 2000; 68(2): 990 - 993.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
R. L. V. Skjot, T. Oettinger, I. Rosenkrands, P. Ravn, I. Brock, S. Jacobsen, and P. Andersen
Comparative Evaluation of Low-Molecular-Mass Proteins from Mycobacterium tuberculosis Identifies Members of the ESAT-6 Family as Immunodominant T-Cell Antigens
Infect. Immun., January 1, 2000; 68(1): 214 - 220.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
A. Demissie, P. Ravn, J. Olobo, T. M. Doherty, T. Eguale, M. Geletu, W. Hailu, P. Andersen, and S. Britton
T-Cell Recognition of Mycobacterium tuberculosis Culture Filtrate Fractions in Tuberculosis Patients and Their Household Contacts
Infect. Immun., November 1, 1999; 67(11): 5967 - 5971.
[Abstract] [Full Text] [PDF]


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