A Mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10).
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 bovis 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 lhp/esat-6 operon, defining a novel gene family. The transcription initiation sites of the lhp/esat-6 operon were mapped using M. tuberculosis RNA. The corresponding promoter signals were not recognized in Mycobacterium smegmatis, in which transcription of lhp/esat-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.
Berthet
Fransois-Xavier
FX
Unite de Genetique MycobactCrienne, lnstitut Pasteur,25 rue du Dr Roux, 75724 Paris cedex 15,France.
Rasmussen
Peter Birk
PB
Department of Tuberculosis Immunology, Statens Seruminstitut, 5 Artilleri vej, DK 2300 Copenhagen S Denmark.
Rosenkrands
Ida
I
Department of Tuberculosis Immunology, Statens Seruminstitut, 5 Artilleri vej, DK 2300 Copenhagen S Denmark.
Andersen
Peter
P
Department of Tuberculosis Immunology, Statens Seruminstitut, 5 Artilleri vej, DK 2300 Copenhagen S Denmark.
Gicquel
Brigitte
B
Unite de Genetique MycobactCrienne, lnstitut Pasteur,25 rue du Dr Roux, 75724 Paris cedex 15,France.
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D007763:Lac Operon; D008969:Molecular Sequence Data; D005810:Multigene Family; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D009876:Operon / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014158:Transcription, Genetic
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins