7/27/2019 Statement Mengenai RD1 _ RD3 Secreted Ag MTB

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Beberapa Statement mengenai RD1 RD3 secretedAg MTB dari beberapa artikel.

1. Advances in mycobacterial genomics in the late 1990s identified an Mtuberculosis genomic segment that is deleted from all strains of BCGvaccine and most environmental mycobacteria, denoted region ofdifference-1(RD1). (GREGORY G. MAHAIRAS, PETER J. SABO, MARK J.HICKEY, DEVINDER C. SINGH, AND C. KENDALL STOVER. Molecular

Analysis of Genetic Differences between Mycobacterium bovis BCG andVirulent M. Bovis. JOURNAL OF BACTERIOLOGY, Mar. 1996, p. 12741282)

2. Three distinct genomic regions of difference (designated RD1 to RD3) werefound to be deleted from BCG, and the precise junctions and DNA sequenceof each deletion were determined. RD3, a 9.3-kb genomic segment present

in virulent laboratory strains of M. bovis and M. tuberculosis, was absentfrom BCG and 84% of virulent clinical isolates. RD2, a 10.7-kb DNA segmentcontaining a novel repetitive element and the previously identified mpt-64gene, was conserved in all virulent laboratory and clinical tubercle bacillitested and was deleted only from substrains derived from the original BCGPasteur strain after 1925. Thus, the RD2 deletion occurred after the originalderivation of BCG. RD1, a 9.5-kb DNA segment found to be deleted from allBCG substrains, was conserved in all virulent laboratory and clinical isolatesofM. bovis and M. tuberculosis tested. The reintroduction of RD1 into BCGrepressed the expression of at least 10 proteins and resulted in a proteinexpression profile almost identical to that of virulent M. bovis and M.tuberculosis, as determined by twodimensional gel electrophoresis. Thesedata indicate a role for RD1 in the regulation of multiple genetic loci,suggesting that the loss of virulence by BCG is due to a regulatorymutation. These findings may be applicable to the rational design of a newattenuated tuberculosis vaccine and the development of new diagnostictests to distinguish BCG vaccination from tuberculosis infection. (GREGORYG. MAHAIRAS, PETER J. SABO, MARK J. HICKEY, DEVINDER C. SINGH, ANDC. KENDALL STOVER. Molecular Analysis of Genetic Differences betweenMycobacterium bovis BCG and Virulent M. Bovis. JOURNAL OFBACTERIOLOGY, Mar. 1996, p. 12741282)

3. One chromosomal region (RD1) was found to be present in 100% of M.

tuberculosis clinical isolates and virulent laboratory strains (H37Rv andErdman) but absent from all BCG substrains. This region encodes esat6 andseven additional ORFs, of which one may be a regulatory gene. (GREGORYG. MAHAIRAS, PETER J. SABO, MARK J. HICKEY, DEVINDER C. SINGH, ANDC. KENDALL STOVER. Molecular Analysis of Genetic Differences betweenMycobacterium bovis BCG and Virulent M. Bovis. JOURNAL OFBACTERIOLOGY, Mar. 1996, p. 12741282)

4. The identification of genetic differences between virulent tubercle bacilliand BCG could also lead to diagnostic tests which can discriminate betweenBCG immunization and infection with virulent tubercle bacilli. It is alsohoped that the identification of critical genetic differences between virulent

and avirulent mycobacteria of the tuberculosis complex will provideinformation about and insights into their pathogenic mechanisms, thus

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7/27/2019 Statement Mengenai RD1 _ RD3 Secreted Ag MTB

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supplying a basis for the development of rational approaches and newtreatments for tuberculosis. (GREGORY G. MAHAIRAS, PETER J. SABO, MARK

J. HICKEY, DEVINDER C. SINGH, AND C. KENDALL STOVER. Molecular

Analysis of Genetic Differences between Mycobacterium bovis BCG andVirulent M. Bovis. JOURNAL OF BACTERIOLOGY, Mar. 1996, p. 12741282)

5. Two proteins encoded by this stretch of DNA, early secretory antigenictarget-6 (ESAT-6) and culture filtrate protein-10 (CFP-10), are strong targetsof Thelper type 1 T cells in patients with M tuberculosis infection. (Lalvani

A, Pathan AA, McShane H, et al. Rapid detection of Mycobacteriumtuberculosis infection by enumeration of antigen-specific T cells. Am JRespir Crit Care Med 2001; 163:824828; Chapman AL, Munkanta M,Wilkinson KA, et al. Rapid detection of active and latent tuberculosisinfection in HIVpositive individuals by enumeration of Mycobacteriumtuberculosis- specific T cells. Aids 2002; 16:22852293)

6. Two of the low-molecular-mass potent T-cell antigens identified byAndersen and colleagues, early secretory antigen target 6 (ESAT-6) andculture filtrate protein 10 (CFP10), are encoded in RD1 (Andersen, P., A. B.

Andersen, A. L. Sorensen, and S. Nagai. 1995. Recall of long-lived immunityto Mycobacterium tuberculosis infection in mice. J. Immunol. 154:33593372; Berthet, F. X., P. B. Rasmussen, I. Rosenkrands, P. Andersen, and B.Gicquel. 1998. A Mycobacterium tuberculosis operon encoding ESAT-6 anda novel low-molecular-mass culture filtrate protein (CFP-10). Microbiology144(Pt 11):31953203) and have been intensively investigated in animalmodels and humans over the last few years.

7. Pengujian Diferensial Hibridisasi array mengidentifikasi 14 regions ofdifference / wilayah perbedaan (RD1-14), mulai ukuran 2-12,7 kb, yangabsen dari bacillus Calmette-Gue'rin Pasteur relatif terhadap M.tuberculosis H37Rv (Gordon, S. V., Brosch, R., Billault, A., Garnier, T.,Eiglmeier, K. & Cole, S. T. (1999) Mol. Microbiol. 32, 643655; Behr, M. A.,Wilson, M. A., Gill, W. P., Salamon, H., Schoolnik, G. K., Rane, S. & Small, P.M. (1999) Science 284, 15201523)

Jl. Salam Damai Raya No. 377,Kayuringin Jaya, Bekasi, Jawa Barat, IndonesiaPhone : (62-21) 71288622Fax : (62-21) 88866220www.nelta.co.id

Marketing Office:Kompleks Sentra Bisnis Blok SB IX No 8,

Harapan Indah, Bekasi, Jawa Barat, Indonesia.Phone/Fax : +62-2188866202 / +62-2188866220

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http://www.nelta.co.id/http://www.nelta.co.id/http://www.nelta.co.id/http://www.nelta.co.id/