• 西藏自治區(qū)人民醫(yī)院( 西藏拉薩 850000);

隨著結(jié)核病防治研究的不斷深入, 人們發(fā)現(xiàn)細胞水平時代結(jié)核病流行病學的兩大問題———傳播途徑和傳染源, 是了解得不夠確切、不夠深刻的, 從傳染與發(fā)病的關(guān)系上鑒定外源性再感染, 用噬菌體分型毫無實際價值。而常規(guī)細菌培養(yǎng)法進行耐藥性監(jiān)測作為流行病學調(diào)查方式之一, 只能了解其耐藥的表型狀況, 難以探討其內(nèi)在機制。隨著分子生物學的飛速發(fā)展, 1980 年以后, 逐步建立了一些根據(jù)核酸序列進行菌株鑒定的高度特異的基因分型方法, 主要包括: 限制性片段長度多態(tài)性、DNA 指紋圖譜分析、脈沖場凝膠電泳、PCR酶切分型、隨機擴增多態(tài)性DNA、DNA 序列分析以及基因芯片技術(shù)等等。結(jié)合現(xiàn)代分子生物信息學技術(shù), 使結(jié)核分枝桿菌的菌株分型進入了一個全新的領(lǐng)域———株水平的鑒定, 也進而使結(jié)核病分子流行病學的研究取得了很大的進展。許多研究者在結(jié)核病的流行病學研究中, 把群體研究與個體研究、宏觀研究與微觀研究結(jié)合起來, 研究結(jié)核分枝桿菌( Mycobacteriumtuberculosis,MTB) 的分子結(jié)構(gòu)上的差異, 結(jié)合病例流行病學資料, 以闡明結(jié)核病的流行病學問題, 形成了結(jié)核病分子流行病學。分子分型技術(shù)是結(jié)核病分子流行病學研究的重要手段之一。對受感染個體的菌株進行分子分型在追蹤傳染源方面起重要作用。

引用本文： 黃麗萍,石荔. 結(jié)核分枝桿菌的株水平鑒定和基因分型技術(shù)研究進展. 中國呼吸與危重監(jiān)護雜志, 2010, 9(2): 216-219. doi: 復制

1. van Embden JD, Cave MD, Crawford JT, et al. Strain identification of Mycobacterium tuberculosis by DNA fingerprinting:recommendations for a standardized methodology. J Clin Microbiol,1993, 31: 406-409.
2. van Soolingen D, De Haas PE, Hermans PW, et al. Comparison of various repetitive DNA elements as genetic markers for strain differentiation and epidemiology of Mycoloacterium tuberculosis. J Clin Microbiol, 1993, 31: 1987-1995.
3. Singh SP, Salamon H, Lahti CJ, et al. Use of pulsed-field gel electrophoresis for molecular epidemiologic and population genetic studies Mycobacterium tuberculosis. J Clin Microbiol, 1999, 37 :1927-1931.
4. van Soolingen D, Qian L, De Haas PE, et al. Predominance of a single genotype of M. tuberculosis in countries of East Asia. J Clin Microbiol, 1995 , 33: 3234-3238.
5. Richner SM, Meiring J, Kirby R. A study of the genetic diversity of Mycobacterium tuberculosis isolated from patients in the eastern province of South Africa using random amplified polymorphic DNA profiling. Electrophoresis, 1997 , 18 : 1570-1576.
6. Rodriguez JC, Royo G, Rodriguez-Valera F. Application of four molecular techniques for typing outbreak-associated Mycobacterium tuberculosis strains. APMIS, 2000, 108 : 231-236.
7. Gonzalez N, Torres MJ, Palomares JC, et al. Characterization of the rpoB gene mutations in clinical isolates of rifampicin-resistant Mycobacterium tuberculosis. Enferm Infecc Microbiol Clin, 1998 ,16: 404-407.
8. Zaza S, Blumberg HM, Beck-Sague C, et al. Nosocomial transmission of M. tuberculosis: role of health care workers in outbreak propagation. J Infect Dis, 1995 , 172: 1542-1549.
9. Orita M, Suzuki Y, Sekiya T, et al. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics, 1989, 5 : 874-879 .
10. Yamazaki T, Haga S, Nakamura RM, et al. Detection of rifampicinresistant strains of Mycobacterium tuberculosis by a non-radioactive PCR-SSCP method. Kekkaku, 1996 , 71: 465-471.
11. Spurgiesz RS, Quitugua TN, Smith KL, et al. Molecular typing of Mycobacterium tuberculosis by using nine novel variable-number tandem repeats across the Beijing family and low-copy-number IS6110 isolates. J Clin Microbiol, 2003, 41 : 4224 -4230 .
12. Pease AC, Solas D, Sullivan EJ, et al. Light-generated oligonucleotide assay for rapid DNA sequence analysis. Proc Natl Acad Sci USA, 1994 , 91: 5022-5026.
13. Van Soolingen D, Qian L, De Haas PE, et al. Predominance of a single genotype of M. tuberculosis in countries of East Asia. J Clin Microbiol, 1995 , 33: 3234-3238.
14. Kato-Maeda M, Rhee JT, Gingeras TR, et al. Comparing genomes within the species Mycobacterium tuberculosis. Genome Res, 2001 ,11: 547-554 .
15. 景奉香, 胡忠義, 孫悅, 等. 用DNA 芯片快速檢測結(jié)核分枝桿菌對利福平的耐藥性. 中華結(jié)核和呼吸雜志, 2001, 24: 551-554 .
16. Godfrey-Faussett P, Githui W, Batchlsr B, et al. Recurrence of HIVrelated tuberculosis in an endemic area may be due to relapse or reinfection. Tuber Lung Dis, 1994, 75 : 199-202.
17. Behr MA, Warren SA, Salamon WH, et al. Transmission of Mycobacterium tuberculosis from smear-negative for acid-fast bacilli. Lancet, 1999, 353: 441 -449.
18. Lemaitre N, Sougakoff W, Truffot-Pernot G, et al. Use of DNA fingerprinting for primary surveillance of nosocomial tuberculosis in a large urban hospital: detection of outbreaks in homeless people and migrant workers. Int J Tuberc Lung Dis, 1998, 2: 390 -396.
19. Zhang Y, Wallace RJ, Mazurek GH. Genetic differences between BCG substrains. Tuber Lung Dis, 1995, 76: 43-50 .
20. van Soolingon D, Qian L, de Haas PEW, et al. Predominance of a single genotype of M. tuberculosis in countries of East Asia. J Clin Microbiol, 1995 , 33: 3234-3238.
21. Palittapongarngin P, Luangsook P, Transuphaswadikul S, et al.Restriction fragment length polymorphism study of Mycobacterium tuberculosis in Thailand using IS6110 as probe. Int J Tuberc Lung Dis, 1997 , 1: 370-376 .
22. Kiers A, Drost AP, van Soolingen D, et al. Use of DNA fingerprinting in international source case finding during a large outbreak of tuberculosis in the Netherland. Int J Tuberc Lung Dis, 1997, 1: 239 -245.
23. Glynn JR, Whiteley J, Bifani PJ, et al. Worldwide occurrence of Beijing /W strains of Mycobacterium tuberculosis: a systematic review. Emerg Infect Dis, 2002, 8 : 843-849 .
24. Moss AR, Alland D, Telzak E, et al. A city-wide outbreak of a multidrug-resistant strains of Mycobacterium tuberculosis in New York. Int J Tuberc Lung Dis, 1997, 1: 115 -121.
25. Wilson RW, Yang ZH, Kelley M, et al. Evidence from molecular fingerprinting of limited spread of drug resistant tuberculosis in Texas. J Clin Microbiol, 1999, 37: 3255-3259.
26. Lemaitre N, Sougakoff W, Truffot-Pemot C, et al. Use of DNA fingerprinting for Primary surveillance of nosoeomial tubereulosis in a large urban hospital: Detection of outbreaks in homeless people and migrant workers. Int J Tub Lung Dis, 1998, 2: 390-396.
27. Jasmer RM, Roemer M, Hamilton J, et al. A prospective, multicenter study of Laboratory cross-contamination of Mycobacterium tubereulosis cultures. Emerg Infect Dis, 2002, 8: 1260-1263.
28. Dye C. Global epidemiology of tubereulosis. Lancet, 2006 , 367: 938 -940.
  1. 1. van Embden JD, Cave MD, Crawford JT, et al. Strain identification of Mycobacterium tuberculosis by DNA fingerprinting:recommendations for a standardized methodology. J Clin Microbiol,1993, 31: 406-409.
  2. 2. van Soolingen D, De Haas PE, Hermans PW, et al. Comparison of various repetitive DNA elements as genetic markers for strain differentiation and epidemiology of Mycoloacterium tuberculosis. J Clin Microbiol, 1993, 31: 1987-1995.
  3. 3. Singh SP, Salamon H, Lahti CJ, et al. Use of pulsed-field gel electrophoresis for molecular epidemiologic and population genetic studies Mycobacterium tuberculosis. J Clin Microbiol, 1999, 37 :1927-1931.
  4. 4. van Soolingen D, Qian L, De Haas PE, et al. Predominance of a single genotype of M. tuberculosis in countries of East Asia. J Clin Microbiol, 1995 , 33: 3234-3238.
  5. 5. Richner SM, Meiring J, Kirby R. A study of the genetic diversity of Mycobacterium tuberculosis isolated from patients in the eastern province of South Africa using random amplified polymorphic DNA profiling. Electrophoresis, 1997 , 18 : 1570-1576.
  6. 6. Rodriguez JC, Royo G, Rodriguez-Valera F. Application of four molecular techniques for typing outbreak-associated Mycobacterium tuberculosis strains. APMIS, 2000, 108 : 231-236.
  7. 7. Gonzalez N, Torres MJ, Palomares JC, et al. Characterization of the rpoB gene mutations in clinical isolates of rifampicin-resistant Mycobacterium tuberculosis. Enferm Infecc Microbiol Clin, 1998 ,16: 404-407.
  8. 8. Zaza S, Blumberg HM, Beck-Sague C, et al. Nosocomial transmission of M. tuberculosis: role of health care workers in outbreak propagation. J Infect Dis, 1995 , 172: 1542-1549.
  9. 9. Orita M, Suzuki Y, Sekiya T, et al. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics, 1989, 5 : 874-879 .
  10. 10. Yamazaki T, Haga S, Nakamura RM, et al. Detection of rifampicinresistant strains of Mycobacterium tuberculosis by a non-radioactive PCR-SSCP method. Kekkaku, 1996 , 71: 465-471.
  11. 11. Spurgiesz RS, Quitugua TN, Smith KL, et al. Molecular typing of Mycobacterium tuberculosis by using nine novel variable-number tandem repeats across the Beijing family and low-copy-number IS6110 isolates. J Clin Microbiol, 2003, 41 : 4224 -4230 .
  12. 12. Pease AC, Solas D, Sullivan EJ, et al. Light-generated oligonucleotide assay for rapid DNA sequence analysis. Proc Natl Acad Sci USA, 1994 , 91: 5022-5026.
  13. 13. Van Soolingen D, Qian L, De Haas PE, et al. Predominance of a single genotype of M. tuberculosis in countries of East Asia. J Clin Microbiol, 1995 , 33: 3234-3238.
  14. 14. Kato-Maeda M, Rhee JT, Gingeras TR, et al. Comparing genomes within the species Mycobacterium tuberculosis. Genome Res, 2001 ,11: 547-554 .
  15. 15. 景奉香, 胡忠義, 孫悅, 等. 用DNA 芯片快速檢測結(jié)核分枝桿菌對利福平的耐藥性. 中華結(jié)核和呼吸雜志, 2001, 24: 551-554 .
  16. 16. Godfrey-Faussett P, Githui W, Batchlsr B, et al. Recurrence of HIVrelated tuberculosis in an endemic area may be due to relapse or reinfection. Tuber Lung Dis, 1994, 75 : 199-202.
  17. 17. Behr MA, Warren SA, Salamon WH, et al. Transmission of Mycobacterium tuberculosis from smear-negative for acid-fast bacilli. Lancet, 1999, 353: 441 -449.
  18. 18. Lemaitre N, Sougakoff W, Truffot-Pernot G, et al. Use of DNA fingerprinting for primary surveillance of nosocomial tuberculosis in a large urban hospital: detection of outbreaks in homeless people and migrant workers. Int J Tuberc Lung Dis, 1998, 2: 390 -396.
  19. 19. Zhang Y, Wallace RJ, Mazurek GH. Genetic differences between BCG substrains. Tuber Lung Dis, 1995, 76: 43-50 .
  20. 20. van Soolingon D, Qian L, de Haas PEW, et al. Predominance of a single genotype of M. tuberculosis in countries of East Asia. J Clin Microbiol, 1995 , 33: 3234-3238.
  21. 21. Palittapongarngin P, Luangsook P, Transuphaswadikul S, et al.Restriction fragment length polymorphism study of Mycobacterium tuberculosis in Thailand using IS6110 as probe. Int J Tuberc Lung Dis, 1997 , 1: 370-376 .
  22. 22. Kiers A, Drost AP, van Soolingen D, et al. Use of DNA fingerprinting in international source case finding during a large outbreak of tuberculosis in the Netherland. Int J Tuberc Lung Dis, 1997, 1: 239 -245.
  23. 23. Glynn JR, Whiteley J, Bifani PJ, et al. Worldwide occurrence of Beijing /W strains of Mycobacterium tuberculosis: a systematic review. Emerg Infect Dis, 2002, 8 : 843-849 .
  24. 24. Moss AR, Alland D, Telzak E, et al. A city-wide outbreak of a multidrug-resistant strains of Mycobacterium tuberculosis in New York. Int J Tuberc Lung Dis, 1997, 1: 115 -121.
  25. 25. Wilson RW, Yang ZH, Kelley M, et al. Evidence from molecular fingerprinting of limited spread of drug resistant tuberculosis in Texas. J Clin Microbiol, 1999, 37: 3255-3259.
  26. 26. Lemaitre N, Sougakoff W, Truffot-Pemot C, et al. Use of DNA fingerprinting for Primary surveillance of nosoeomial tubereulosis in a large urban hospital: Detection of outbreaks in homeless people and migrant workers. Int J Tub Lung Dis, 1998, 2: 390-396.
  27. 27. Jasmer RM, Roemer M, Hamilton J, et al. A prospective, multicenter study of Laboratory cross-contamination of Mycobacterium tubereulosis cultures. Emerg Infect Dis, 2002, 8: 1260-1263.
  28. 28. Dye C. Global epidemiology of tubereulosis. Lancet, 2006 , 367: 938 -940.