吉林省结核分枝杆菌oxyR-ahpC基因耐药相关性研究
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摘要
目的阐明吉林省结核分枝杆菌耐异烟肼的临床分离株中oxyR-ahpC基因间隔区突变特点。方法对580株结核分枝杆菌临床分离株(耐异烟肼菌株500株;异烟肼敏感株80株)的DNA片断扩增及DNA序列分析,并将测序所得结果与标准菌株的DNA序列进行对比分析。结果 580株结核分枝杆菌临床菌株中,80株敏感株oxyR-ahpC间隔区未发生突变;在500株异烟肼耐药的临床分离株中有200株菌株中存在oxyR-ahpC间隔区突变,其中有29株在(-17)位点发生突变,12株在(-27)位点发生突变,134株在11位点发生突变。结论吉林省耐多药结核分枝杆菌异烟肼耐药基因中oxyR-ahpC间隔区突变具有明显的区域特异性,建议在本省的结核病耐多药快速检测项目中增加对oxyR-ahpC间隔区突变的检测,以便提高耐多药患者的检出率。
Objective To elucidate the characteristics of oxyR-ahpC gene spacer mutations in clinical isolates of Mycobacterium tuberculosis in Jilin. Methods The DNA fragment amplification and DNA sequence analysis of 580 strains of Mycobacterium tuberculosis clinical isolates(500 strains resistant to isoniazid resistant strains, 80 isoniazid sensitive strains) were analyzed, and the results were compared with the DNA sequence of the standard strains. Results Among 580 strains of Mycobacterium tuberculosis, 80 sensitive strains were not mutated in the oxyR-ahpC interval. In 500 strains of isoniazid resistant isolates, oxyR-ahpC spacer mutations were found in 200 strains of clinical isolates,(-17) locus mutation in 29 strains,(-27) loci mutations in 12 strains, 11 locus mutation in 134 strains. Conclusion The oxyR-ahpC septum mutation in the multidrug resistant isoniazid resistant gene of Mycobacterium tuberculosis in Jilin province has obvious regional specificity. It is suggested to increase the detection of oxyR-ahpC septum mutation in the rapid detection of multidrug resistance of tuberculosis, so as to improve the detection rate of multidrug resistant patients.
Objective To elucidate the characteristics of oxyR-ahpC gene spacer mutations in clinical isolates of Mycobacterium tuberculosis in Jilin. Methods The DNA fragment amplification and DNA sequence analysis of 580 strains of Mycobacterium tuberculosis clinical isolates(500 strains resistant to isoniazid resistant strains, 80 isoniazid sensitive strains) were analyzed, and the results were compared with the DNA sequence of the standard strains. Results Among 580 strains of Mycobacterium tuberculosis, 80 sensitive strains were not mutated in the oxyR-ahpC interval. In 500 strains of isoniazid resistant isolates, oxyR-ahpC spacer mutations were found in 200 strains of clinical isolates,(-17) locus mutation in 29 strains,(-27) loci mutations in 12 strains, 11 locus mutation in 134 strains. Conclusion The oxyR-ahpC septum mutation in the multidrug resistant isoniazid resistant gene of Mycobacterium tuberculosis in Jilin province has obvious regional specificity. It is suggested to increase the detection of oxyR-ahpC septum mutation in the rapid detection of multidrug resistance of tuberculosis, so as to improve the detection rate of multidrug resistant patients.
引文
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[15] Raviglione MC,Smith IM.XDR tuberculosis-implications for global public health[J].New Engl J Med,2007,356(7):356-359.
[16] Srinivas V,Ramaswamy SV,Reich R,et al.Single nucleotide polymorphisms in genes associated with isoniazid resistance in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2003,47(4):1241-1250.
[17] Doustdar F,Khosravia D,Fsrnia P,et al.Molecular analysis of isoniazid resistance in differernt genotypes of Mycobacterium tuberculosis isolates from Iran[J].Microb Drug Resist,2008,14(4):273-279.
[18] Mukaigawa J,Endoh M,Yanagawa Y,et al.Anti-drug pattern of drug-resistant Mycobacterium tuberculosis and analysis of mutation in drug-target genes[J].Kansenshogaku Zasshi,2005,79(6):388-396.
[19] Pang Y,Xia H,Zhang Z,et al.Multicenter evalution of genechip for detection of multidrug-resistant Mycobacterium tuberculosis[J].Clin Microbiol,2013,51(6):1707-1713.
[20] 张炜煜,杨修军,王慧,等.吉林省耐多药结核分枝杆菌rpoB及katG基因突变特征分析[J].中国实验诊断学,2017,21(10):1731-1735.
[2] 陈曦,马玛,金奇,等.耐异烟肼结核分枝杆菌临床分离株耐药相关基因突变研究[J].中华结核和呼吸杂志,2005,28(4):250-253.
[3] Ramaswamy SV,Reich R,Doll SJ,et al.Sirlgle nudeotide polymorphisms in genes associated with isoniazid resistance in Mycobaaenitm tubereulosis[J].Antimicrob Agents Chemother,2003,47(4):1241-1250.
[4] 赵雁林,王黎霞,成诗明,等.结核分枝杆菌药物敏感性试验标准化操作程序及质量保证手册[M].北京:人民卫生出版社,2013:24-30.
[5] 赵雁林,王黎霞,成诗明,等.分枝杆菌分离培养标准化操作程序及质量保证手册[M].北京:人民卫生出版社,2013:2.
[6] 逄宇,夏辉,姜广路,等.中国结核分枝杆菌寡核苷酸基因分型及其耐药性分析[J].中华检验医学杂志,2011,34(11):1023-1028.
[7] 徐建国,阚飚,张建中,等.现场细菌学[M].北京:科学出版社,2011:411-465.
[8] Kiepiela P,Bishop KS,Smith AN,et al.Genomic metations in the katG,inhA and aphC genes are useful for the prediction of isoniazid resistance in Mycobacterium tuberculosis isolates form Kwazulu Natal,South Africa[J].Tuber Lung Disl,2000,80(1):47-56.
[9] Wilson TM,Collins DM.aphC,a gene involved in isoniazid resistance of the Mycobacterium tuberculosis complex[J].Mol Microbiol,1996,19(5):1025-1034.
[10] Mukaigawa J,Endoh M,Yanagawa Y.Anti-drug pattern of drug resistance Mycobacterium tuberculosis and analysis of mutation in drug target genes[J].Kansenshogaku Zasshi,2005,79(6):388-396.
[11] Viader-salvado JM,Luna-Aguirre CM,Reyes-Ruiz JM,et al.Frequency of mutations in ropB and condons 315 and 463 of katG in rifampin and/or isoniazid-resistant Mycobacterium tuberculosis isolates form northeast Mexico[J].Micorb Drug Resist,2003,9(1):33-38.
[12] Cardoso RF,Cooksey RC,Morlock GP,et al.Screening and characterization of mutations in isoniazid-resistant Mycobacterium tuberculosis isolates from Brazil[J].Antimicrob Agents Chemother,2004,48(9):3373-3381.
[13] Lee AS,Teo AS,Wong SY.Novel mutations in ndh in isoniazid-resistant Mycobacterium tuberculosis isolates[J].Antimicrob Agentes Chemother,2001,45(7):2157-2159.
[14] Zhang M,Yue J,Yang Y,et al.Detection of mutations associated with isoniazid resistance in Mycobacterium tuberculosis isolates from China[J].J Clin Microbiol,2005,43(11):5477-5482.
[15] Raviglione MC,Smith IM.XDR tuberculosis-implications for global public health[J].New Engl J Med,2007,356(7):356-359.
[16] Srinivas V,Ramaswamy SV,Reich R,et al.Single nucleotide polymorphisms in genes associated with isoniazid resistance in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2003,47(4):1241-1250.
[17] Doustdar F,Khosravia D,Fsrnia P,et al.Molecular analysis of isoniazid resistance in differernt genotypes of Mycobacterium tuberculosis isolates from Iran[J].Microb Drug Resist,2008,14(4):273-279.
[18] Mukaigawa J,Endoh M,Yanagawa Y,et al.Anti-drug pattern of drug-resistant Mycobacterium tuberculosis and analysis of mutation in drug-target genes[J].Kansenshogaku Zasshi,2005,79(6):388-396.
[19] Pang Y,Xia H,Zhang Z,et al.Multicenter evalution of genechip for detection of multidrug-resistant Mycobacterium tuberculosis[J].Clin Microbiol,2013,51(6):1707-1713.
[20] 张炜煜,杨修军,王慧,等.吉林省耐多药结核分枝杆菌rpoB及katG基因突变特征分析[J].中国实验诊断学,2017,21(10):1731-1735.