遗传 ›› 2016, Vol. 38 ›› Issue (10): 928-939.doi: 10.16288/j.yczz.16-138
刘洋1, 2, 王邦兴1, 刘志永1, 韩轶1, 谭耀驹3, 李昕洁3, 刘健雄3, 谭守勇3, 张天宇1
收稿日期:2016-04-20
修回日期:2016-07-14
出版日期:2016-10-20
发布日期:2016-10-20
作者简介:谭守勇,硕士,主任医师,研究方向：呼吸内科学。张天宇,博士,研究员,研究方向：药学和传染病学。
基金资助:Yang Liu1, 2, Bangxing Wang1, Zhiyong Liu1, Yi Han1, Yaoju Tan3, Xinjie Li3, Jianxiong Liu3, Shouyong Tan3, Tianyu Zhang1
Received:2016-04-20
Revised:2016-07-14
Online:2016-10-20
Published:2016-10-20
Supported by:摘要： 结核病(Tuberculosis, TB)至今仍是世界三大传染疾病之一。2014年,TB导致的死亡人数已经超过HIV。二线抗TB药物是临床治疗耐多药TB(Multidrug-resistant TB, MDR-TB)的主要药物,然而某些MDR-TB患者由于未及时诊断、治疗方案不合理、所处区域医疗条件差等原因,逐渐发展成为广泛耐药TB(Extensively drug-resistant TB, XDR-TB),使治疗更加困难,其死亡率甚至与肺癌接近。目前结核分枝杆菌(Mycobacterium tuberculosis)的耐药性机制研究已经转向非一线药物,如二线、三线和一些新研发的抗TB药物,揭示这些非一线药物的耐药机制对于耐药TB的治疗和新型抗TB药物的研发具有重要意义。本文对目前临床上使用的主要非一线药物的耐药机制研究进行了综述,并对目前常用的TB耐药性诊断方法的优缺点进行了归纳比较。
刘洋, 王邦兴, 刘志永, 韩轶, 谭耀驹, 李昕洁, 刘健雄, 谭守勇, 张天宇. 非一线抗结核药物耐药机制及耐药性诊断研究进展[J]. 遗传, 2016, 38(10): 928-939.
Yang Liu, Bangxing Wang, Zhiyong Liu, Yi Han, Yaoju Tan, Xinjie Li, Jianxiong Liu, Shouyong Tan, Tianyu Zhang. Progress in resistance mechanisms and diagnosis of non-first line anti-TB drugs[J]. Hereditas(Beijing), 2016, 38(10): 928-939.
| [1] World Health Organization. Global tuberculosis report 2015. Geneva: World Health Organization, 2015. [2] Technical Guidance Group of the Fifth National TB Epidemiological Survey, the Office of the Fifth National TB Epidemiological Survey. The fifth national tuberculosis epidemiological survey in 2010. Chin J Antituberc , 2012, 34(8): 485-508. 全国第五次结核病流行病学抽样调查技术指导组, 全国第五次结核病流行病学抽样调查办公室. 2010年全国第五次结核病流行病学抽样调查报告. 中国防痨杂志, 2012, 34(8): 485-508. [3] Van Rie A, Enarson D. XDR tuberculosis: an indicator of public-health negligence. Lancet , 2006, 368(9547): 1554- 1556. [4] Iseman MD. Evolution of drug-resistant tuberculosis: A tale of two species. Proc Natl Acad Sci USA , 1994, 91(7): 2428-2429. [5] Zhao YL, Xu SF, Wang LX, Chin DP, Wang SF, Jiang GL, Xia H, Zhou Y, Li Q, Ou XC, Pang Y, Song YY, Zhao B, Zhang HT, He GX, Guo J, Wang Y. National survey of drug-resistant tuberculosis in China. N Engl J Med , 2012, 366(23): 2161-2170. [6] Migliori GB, De Iaco G, Besozzi G, Centis R, Cirillo DM. First tuberculosis cases in Italy resistant to all tested drugs. Euro Surveill , 2007, 12(5): E070517. [7] Klopper M, Warren RM, Hayes C, van Pittius NCG, Streicher EM, Müller B, Sirgel FA, Chabula-Nxiweni M, Hoosain E, Coetzee G, van Helden PD, Victor TC, Trollip AP. Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa. Emerg Infect Dis , 2013, 19(3): 449-455. [8] Udwadia ZF, Amale RA, Ajbani KK, Rodrigues C. Totally drug-resistant tuberculosis in India. Clin Infect Dis , 2012, 54(4): 579-581. [9] ZumLa A, Nahid P, Cole ST. Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discov , 2013, 12(5): 388-404. [10] Wong SY, Lee JS, Kwak HK, Via LE, Boshoff HIM, Barry CE. Mutations in gidB confer low-level streptomycin resistance in Mycobacterium tuberculosis . Antimicrob Agents Chemother , 2011, 55(6): 2515-2522. [11] Gao Q, Huang HH. Update on antimicrobial resistance in Clostridium difficile . Hereditas ( Beijing ), 2015, 37(5): 458-464. 高琼, 黄海辉. 艰难梭菌耐药性及耐药机制研究进展. 遗传, 2015, 37(5): 458-464. [12] Long QX, He Y, Xie JP. The molecular physiological and genetic mechanisms underlying the superb efficacy of quinolones. Acta Pharm Sin , 2012, 47(8): 969-977. 龙泉鑫, 何颖, 谢建平. 喹诺酮类药物作用的生理和遗传的分子机制. 药学学报, 2012, 47(8): 969-977. [13] Zhang S, Chen JZ, Cui P, Shi WL, Zhang WH, Zhang Y. Identification of novel mutations associated with clofazimine resistance in Mycobacterium tuberculosis . J Antimicrob Chemother , 2015, 70(9): 2507-2510. [14] Pantel A, Petrella S, Veziris N, Brossier F, Bastian S, Jarlier V, Mayer C, Aubry A. Extending the definition of the GyrB quinolone resistance-determining region in Mycobacterium tuberculosis DNA gyrase for assessing fluoroquinolone resistance in M . tuberculosis . Antimicrob Agents Chemother , 2012, 56(4): 1990-1996. [15] Berning SE. The role of fluoroquinolones in tuberculosis today. Drugs , 2001, 61(1): 9-18. [16] Bozeman L, Burman W, Metchock B, Welch L, Weiner M, Consortium TT. Fluoroquinolone susceptibility among Mycobacterium tuberculosis isolates from the United States and Canada. Clin Infect Dis , 2005, 40(3): 386-391. [17] Wang HY, Wang Y, Yu CB, Zuo Y, Wang JL, Liu ZM. Study of the status of drug resistant tuberculosis in 12 counties in Shandong. Prev Med Trib , 2008, 14(12): 1075-1076, 1080. 王海英, 王燕, 于春宝, 左云, 王俊玲, 刘志敏. 2004~ 2007年山东省部分结核分枝杆菌耐药情况检测分析. 预防医学论坛, 2008, 14(12): 1075-1076, 1080. [18] Zhang GL, Du CM, Takuya K, Wang W, Shi RR. China-Japan cooperation project on second line tuberculosis drug resistance survey in Henan Province. J Med Forum , 2005, 26(19): 14-16. 张国龙, 杜长梅, 苍泽卓也, 池田雄史, 王伟, 石瑞如. 中日合作对河南省结核菌二线药物耐药监测研究. 医药论坛杂志, 2005, 26(19): 14-16. [19] Pan XQ, Xu DF, Wang DP, Chai H, Yu SQ, Wang Q. Drug resistance of 251 strains of multidrug resistant Mycobacterium tuberculosis to second-line drugs. Anhui Med Pharm J , 2012, 16(9): 1339-1340. 潘学琴, 徐东方, 王东萍, 柴华, 於淑琦, 王庆. 251株耐多药结核分枝杆菌二线药耐药结果分析. 安徽医药, 2012, 16(9): 1339-1340. [20] Schatz A, Bugle E, Waksman SA. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Exp Biol Med , 1944, 55(1): 66-69. [21] Cuevas-Córdoba B, Cuellar-Sánchez A, Pasissi-Crivelli A, Santana-Álvarez CA, Hernández-Illezcas J, Zenteno-Cuevas R. rrs and rpsL mutations in streptomycin-resistant isolates of Mycobacterium tuberculosis from Mexico. J Microbiol Immunol Infect , 2013, 46(1): 30-34. [22] Sreevatsan S, Pan X, Stockbauer KE, Williams DL, Kreiswirth BN, Musser JM. Characterization of rpsL and rrs mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from diverse geographic localities. Antimicrob Agents Chemother , 1996, 40(4): 1024-1026. [23] Smittipat N, Juthayothin T, Billamas P, Jaitrong S, Rukseree K, Dokladda K, Chaiyasirinroje B, Disratthakit A, Chaiprasert A, Mahasirimongkol S, Yanai H, Yamada N, Tokunaga K, Palittapongarnpim P. Mutations in rrs , rpsL and gidB in streptomycin-resistant Mycobacterium tuberculosis isolates from Thailand. J Glob Antimicrob Res , 2016, 4: 5-10. [24] Heifets L, Simon J, Pham V. Capreomycin is active against non-replicating M . tuberculosis . Ann Clin Microb Anti , 2005, 4(1): 6. [25] Maus CE, Plikaytis BB, Shinnick TM. Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis . Antimicrob Agents Chemother , 2005, 49(8): 3192-3197. [26] Du QL, Dai GM, Long QX, Yu X, Dong LL, Huang HR, Xie JP. Mycobacterium tuberculosis rrs A1401G mutation correlates with high-level resistance to kanamycin, amikacin, and capreomycin in clinical isolates from mainland China. Diagnost Microbiol Infect Dis , 2013, 77(2): 138-142. [27] Chang S, Fu YH, Li Q, Bu JL, Huang HR, Ma Y, Chen XY. Analysis on drug resistance and cross resistance of Mycobacterium tuberculosis isolated from clinical samples to four injectable antituberculous drugs. Chin J Antituberc , 2013, 35(1): 37-40 常珊, 付育红, 李琦, 卜建玲, 黄海荣, 马玙, 陈效友. 结核分枝杆菌临床分离株对四种注射用抗结核药物耐药及交叉耐药分析. 中国防痨杂志, 2013, 35(1): 37-40. [28] Wang L, Shi XD. Activity of four amino glycosides antibiotics against Mycobacterium tuberculosis in vitro . Exp Lab Med , 2009, 27(4): 367-368. 王雷, 施旭东. 4种氨基甙类抗生素对结核分枝杆菌(MTB)的体外抑菌作用的研究. 实验与检验医学, 2009, 27(4): 367-368. [29] Jugheli L, Bzekalava N, de Rijk P, Fissette K, Portaels F, Rigouts L. High level of cross-resistance between kanamycin, amikacin, and capreomycin among Mycobacterium tuberculosis isolates from Georgia and a close relation with mutations in the rrs gene. Antimicrob Agents Chemother , 2009, 53(12): 5064-5068. [30] Via LE, Cho SN, Hwang S, Bang H, Park SK, Kang HS, Jeon D, Min SY, Oh T, Kim Y, Rajan V, Wong SY, Shamputa IC, Carroll M, Goldfeder L, Lee SA, Holland SM, Eum S, Lee H, Barry CE III. Polymorphisms associated with resistance and cross-resistance to aminoglycosides and capreomycin in Mycobacterium tuberculosis isolates from South Korean Patients with drug-resistant tuberculosis. J Clin Microbiol , 2010, 48(2): 402-411. [31] Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, Collins D, de Lisle G, Jacobs W Jr. inhA , a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis . Science , 1994, 263(5144): 227-230. [32] Vilchèze C, Weisbrod TR, Chen B, Kremer L, Hazbón MH, Wang F, Alland D, Sacchettini JC, Jacobs WR Jr. Altered NADH/NAD + ratio mediates coresistance to isoniazid and ethionamide in mycobacteria. Antimicrob Agents Chemother , 2005, 49(2): 708-720. [33] De Kantor IN, Barrera L. Susceptibility tests to second line drugs and re-treatment of tuberculosis. Revisiting early experiences. Medicina , 2007, 67(3): 231-237. [34] Vilchèze C, Wang F, Arai M, Hazbón MH, Colangeli R, Kremer L, Weisbrod TR, Alland D, Sacchettini JC, Jacobs WR Jr. Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid. Nat Med , 2006, 12(9): 1027-1029. [35] Larsen MH, Vilchèze C, Kremer L, Besra GS, Parsons L, Salfinger M, Heifets L, Hazbon MH, Alland D, Sacchettini JC, Jacobs WR Jr. Overexpression of inhA , but not kasA , confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis , M . bovis BCG and M . tuberculosis . Mol Microbiol , 2002, 46(2): 453-466. [36] Cáceres NE, Harris NB, Wellehan JF, Feng Z, Kapur V, Barletta RG. Overexpression of the D-alanine racemase gene confers resistance to D-cycloserine in Mycobacterium smegmatis . J Bacteriol , 1997, 179(16): 5046-5055. [37] Feng ZY, Barletta RG. Roles of Mycobacterium smegmatis D-alanine: D-alanine ligase and D-alanine racemase in the mechanisms of action of and resistance to the peptidoglycan inhibitor D-cycloserine. Antimicrob Agents Chemother , 2003, 47(1): 283-291. [38] Chen JM, Uplekar S, Gordon SV, Cole ST. A point mutation in cycA partially contributes to the D-cycloserine resistance trait of Mycobacterium bovis BCG vaccine strains. PLoS One , 2012, 7(8): e43467. [39] Mitnick C, Bayona J, Palacios E, Shin S, Furin J, Alcántara F, Sánchez E, Sarria M, Becerra M, Fawzi MCS, Kapiga S, Neuberg D, Maguire JH, Kim JY, Farmer P. Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru. N Engl J Med , 2003, 348(2): 119-128. [40] Mathys V, Wintjens R, Lefevre P, Bertout J, Singhal A, Kiass M, Kurepina N, Wang XM, Mathema B, Baulard A, Kreiswirth BN, Bifani P. Molecular genetics of para -aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosis . Antimicrob Agents Chemother , 2009, 53(5): 2100-2109. [41] Sotgiu G, Pontali E, Migliori GB. Linezolid to treat MDR-/XDR-tuberculosis: available evidence and future scenarios. Eur Respir J , 2015, 45(1): 25-29. [42] Curtin ÁC, De Angelis M, Cipriani M, Corbo M, McSweeney PLH, Gobbetti M. Amino acid catabolism in cheese-related bacteria: selection and study of the effects of pH, temperature and NaCl by quadratic response surface methodology. J Appl Microbiol , 2001, 91(2): 312- 321. [43] Koh WJ, Kwon OJ, Gwak H, Chung JW, Cho SN, Kim WS, Shim TS. Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis. J Antimicrob Chemother , 2009, 64(2): 388-391. [44] Makafe GG, Cao YY, Tan YJ, Julius M, Liu ZY, Wang CW, Njire MM, Cai XS, Liu TZ, Wang BX, Pang W, Tan SY, Zhang BC, Yew WW, Lamichhane G, Guo JT, Zhang TY. Oxazolidinone resistance in Mycobacterium tuberculosis : what is the role of Cys154Arg mutation in the ribosomal protein L3? Antimicrob Agents Chemother , 2016, doi:10.1128/AAC.00152-16. [45] Diacon AH, Pym A, Grobusch MP, de los Rios JM, Gotuzzo E, Vasilyeva I, Leimane V, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, De Paepe E, van Heeswijk RPG, Dannemann B. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med , 2014, 371(8): 723-732. [46] Andries K, Verhasselt P, Guillemont J, Göhlmann HWH, Neefs JM, Winkler H, Van Gestel J, Timmerman P, Zhu M, Lee E, Williams P, De Chaffoy D, Huitric E, Hoffner S, Cambau E, Truffot-Pernot C, Lounis N, Jarlier V. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis . Science , 2005, 307(5707): 223- 227. [47] Zhang T, Li S Y, Williams K N, Williams, K. N., Andries, K., & Nuermberger, E. L. Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection. Am J Resp Crit Care, 2011, 184(6): 732-737. [48] Koul A, Vranckx L, Dendouga N, Balemans W, Van Den Wyngaert I, Vergauwen K, Göhlmann HWH, Willebrords R, Poncelet A, Guillemont J, Bald D, Andries K. Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis. J Biol Chem , 2008, 283(37): 25273-25280. [49] Mothiba MT, Anderson R, Fourie B, Germishuizen WA, Cholo MC. Effects of clofazimine on planktonic and biofilm growth of Mycobacterium tuberculosis and Mycobacterium smegmatis . J Glob Antimicrob Re , 2015, 3(1): 13-18. [50] Field SK, Cowie RL. Treatment of Mycobacterium avium- intracellulare complex lung disease with a macrolide, ethambutol, and clofazimine. Chest , 2003, 124(4): 1482- 1486. [51] du Toit LC, Pillay V, Danckwerts MP. Tuberculosis chemotherapy: current drug delivery approaches. Respir Res , 2006, 7(1): 118. [52] Mukherjee JS, Rich ML, Socci AR, Joseph JK, Virú FA, Shin SS, Furin JJ, Becerra MC, Barry DJ, Kim JY, Bayona J, Farmer P, Fawzi MCS, Seung KJ. Programmes and principles in treatment of multidrug-resistant tuberculosis. Lancet , 2004, 363(9407): 474-481. [53] Cholo MC, Steel HC, Fourie PB, Germishuizen WA, Anderson R. Clofazimine: current status and future prospects. J Antimicrob Chemother , 2012, 67(2): 290-298. [54] Hartkoorn RC, Uplekar S, Cole ST. Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis . Antimicrob Agents Chemother , 2014, 58(5): 2979-2981. [55] Musser JM, Kapur V, Williams DL, Kreiswirth BN, van Soolingen D, van Embden JDA. Characterization of the catalase-peroxidase gene ( katG ) and inhA locus in isoniazid-resistant and -susceptible strains of Mycobacterium tuberculosis by automated DNA sequencing: restricted array of mutations associated with drug resistance. J Infect Dis , 1996, 173(1): 196-202. [56] Zhao F, Wang XD, Erber LN, Luo M, Guo AZ, Yang SS, Gu J, Turman BJ, Gao YR, Li DF, Cui ZQ, Zhang ZP, Bi LJ, Baughn AD, Zhang XE, Deng JY. Binding pocket alterations in dihydrofolate synthase confer resistance to para -aminosalicylic acid in clinical isolates of Mycobacterium tuberculosis . Antimicrob Agents Chemother , 2014, 58(3): 1479-1487. [57] Parish T, Stoker NG. Use of a flexible cassette method to generate a double unmarked Mycobacterium tuberculosis tlyA plcABC mutant by gene replacement. Microbiology , 2000, 146(8): 1969-1975. [58] Siddiqi N, Das R, Pathak N, Banerjee S, Ahmed N, Katoch VM, Hasnain SE. Mycobacterium tuberculosis isolate with a distinct genomic identity overexpresses a tap-like efflux pump. Infection , 2004, 32(2): 109-111. [59] Liu J, Takiff HE, Nikaido H. Active efflux of fluoroquinolones in Mycobacterium smegmatis mediated by LfrA , a multidrug efflux pump. J Bacteriol , 1996, 178(13): 3791- 3795. [60] Velayati AA, Farnia P, Ibrahim TA, Haroun RZ, Kuan HO, Ghanavi J, Farnia P, Kabarei AN, Tabarsi P, Omar A, Varahram M, Masjedi MR. Differences in cell wall thickness between resistant and nonresistant strains of Mycobacterium tuberculosis : using transmission electron microscopy. Chemotherapy , 2009, 55(5): 303-307. [61] Cunningham AF, Spreadbury CL. Mycobacterial stationary phase induced by low oxygen tension: cell wall thickening and localization of the 16-kilodalton α-crystallin homolog. J Bacteriol , 1998, 180(4): 801-808. [62] Wayne LG, Hayes LG. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun , 1996, 64(6): 2062-2069. [63] Hegde SS, Vetting MW, Roderick SL, Mitchenall LA, Maxwell A, Takiff HE, Blanchard JS. A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science , 2005, 308(5727): 1480-1483. [64] Md Mahmudul Islam, H.M. Adnan Hameed, Julius Mugweru, Chiranjibi Chhotaray, Wang CW, Tan YJ, Liu JX, Li XJ, Tan SY, Iwao Ojima, Wing WY, Zhang TY. Drug resistance mechanisms and novel drug targets for tuberculosis therapy. J Genet Genomics , 2016, doi:10.1016/j.jgg. 2016.10.002. [65] Kim SJ. Drug-susceptibility testing in tuberculosis: methods and reliability of results. Eur Respir J , 2005, 25(3): 564-569. [66] Hanna BA, Ebrahimzadeh A, Elliott LB, Morgan MA, Novak SM, Rusch-Gerdes S, Acio M, Dunbar DF, Holmes TM, Rexer CH, Savthyakumar C, Vannier AM. Multicenter evaluation of the BACTEC MGIT 960 system for recovery of mycobacteria. J Clin Microbiol , 1999, 37(3): 748-752. [67] Huang TS, Lee SSJ, Tu HZ, Huang WK, Chen YS, Huang CK, Wann SR, Lin HH, Liu YC. Use of MGIT 960 for rapid quantitative measurement of the susceptibility of Mycobacterium tuberculosis complex to ciprofloxacin and ethionamide. J Antimicrob Chemother , 2004, 53(4): 600- 603. [68] Lu JM, Wang J, Huang XC, Hu ZY, Cui ZL. Evaluation of microscopic observation drug susceptibility for drug susceptibility testing of Mycobacterium tuberculosis in smear- positive sputum. Chin J Prev Med , 2011, 45(1): 21-25. 陆俊梅, 王洁, 黄晓辰, 胡忠义, 崔振玲. 显微镜观察药物敏感性检测技术在痰标本直接药敏试验中的应用. 中华预防医学杂志, 2011, 45(1): 21-25. [69] Shen XN, Zhao YL, Xiao HP. Research progress of phenotype detection of Mycobacterium tuberculosis drug susceptibility. Chin J Antituberc , 2013, 35(6): 463-467. 申晓娜, 赵雁林, 肖和平. 结核分枝杆菌药物敏感性表型检测的研究进展. 中国防痨杂志, 2013, 35(6): 463-467. [70] Jacobs WR Jr, Barletta RG, Udani R, Chan J, Kalkut G, Sosne G, Kieser T, Sarkis GJ, Hatfull GF, Bloom BR. Rapid assessment of drug susceptibilities of Mycobacterium tuberculosis by means of luciferase reporter phages. Science , 1993, 260(5109): 819-822. [71] Isfahani BN, Tavakoli A, Salehi M, Tazhibi M. Detection of rifampin resistance patterns in Mycobacterium tuberculosis strains isolated in Iran by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing methods. Mem Inst Oswaldo Cruz , 2006, 101(6): 597-602. [72] Conn RB, Charache P, Chappelle EW. Limits of applicability of the firefly luminescence ATP assay for the detection of bacteria in clinical specimens. Am J Clin Pathol , 1975, 63(4): 493-501. [73] Yan ZQ, Yang SL, Gong Y. Use of PCR related methods in detection of gene mutation. Hereditas ( Beijing ), 2003, 25(2): 198-200. 颜志强, 杨胜利, 龚毅. PCR及其衍生技术在基因突变检测中的应用. 遗传, 2003, 25(2): 198-200. [74] Xu ZY, Bao QY, Niu YX. Factors that influence direct sequencing of PCR products. Hereditas ( Beijing ), 2002, 24(5): 548-550. 徐祖元, 包其郁, 牛宇欣. PCR产物直接测序技术中影响因素的研究. 遗传, 2002, 24(5): 548-550. [75] Xu P, Gan MY, Gao Q. Current applications of next-generation sequencing technology in Mycobacterium tuberculosis research. J Microb Infect , 2015, 10(1): 54-60. 徐鹏, 甘明宇, 高谦. 二代测序技术在结核分枝杆菌研究中的应用进展. 微生物与感染, 2015, 10(1): 54-60. [76] Li WK, Li FY, Zhang SY, Cai B, Zheng N, Nie Y, Zhou D, Zhao Q. Automatic analysis pipeline of next-generation sequencing data. Hereditas ( Beijing ), 2014, 36(6): 618- 624. 李文轲, 李丰余, 张思瑶, 蔡斌, 郑娜, 聂宇, 周到, 赵倩. 基因组二代测序数据的自动化分析流程. 遗传, 2014, 36(6): 618-624. [77] Wu XQ, Lu Y, Zhang JX, Liang JQ, Zhang GY, Li HM, Lü CH, Ding BC. Detection of streptomycin resistance in Mycobacterium tuberculosis clinical isolates using four molecular methods in China. Acta Genet Sin , 2006, 33(7): 655-663. [78] Helb D, Jones M, Story E, Boehme C, Wallace E, Ho K, Kop J, Owens MR, Rodgers R, Banada P, Safi H, Blakemore R, Lan NTN, Jones-López EC, Levi M, Burday M, Ayakaka I, Mugerwa RD, McMillan B, Winn-Deen E, Christel L, Dailey P, Perkins MD, Persing DH, Alland D. Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J Clin Microbiol , 2010, 48(1): 229-237. [79] Ajbani K, Nikam C, Kazi M, Gray C, Boehme C, Balan K, Shetty A, Rodrigues C. Evaluation of genotype MTBDRsl assay to detect drug resistance associated with fluoroquinolones, aminoglycosides and ethambutol on clinical sediments. PLoS One , 2012, 7(11): e49433. [80] World Health Organization. The use of molecular line probe assay for the detection of resistance to second-line anti-tuberculosis drugs: expert group meeting report. Geneva: World Health Organization, 2013. |
| [1] | 张沥元, 黄芙静, 许峻旗, 龚真, 谢建平. 结核分枝杆菌酸抗性基因及其调控网络[J]. 遗传, 2018, 40(7): 546-560. |
| [2] | 祝力骋,卢俊婉,王建,许腾,徐娟华. 肺炎克雷伯菌blaCARB-2基因的分布及结构分析[J]. 遗传, 2018, 40(7): 593-600. |
| [3] | 黄莹,刘琪,池连江,石承民,吴祯,胡敏,石宏,陈华. BIG-Annotator：基因组测序数据高效功能注释及其在遗传诊断中的应用[J]. 遗传, 2018, 40(11): 1015-1023. |
| [4] | 刘福林, 周瑾, 张蔚, 汪晖. 胎盘发育过程中的表观遗传学改变及其相关疾病[J]. 遗传, 2017, 39(4): 263-275. |
| [5] | 邹永新,龚瑶琴. 影响RNA剪接的基因变异[J]. 遗传, 2017, 39(3): 200-207. |
| [6] | 易灵娴,刘艺云,吴仁杰,梁梓森,刘健华. 质粒介导的黏菌素耐药基因mcr-1研究进展[J]. 遗传, 2017, 39(2): 110-126. |
| [7] | 杨盛智, 吴国艳, 龙梅, 邓雯文, 王红宁, 邹立扣. 鸡蛋生产链中沙门氏菌对抗生素及消毒剂的耐药性研究[J]. 遗传, 2016, 38(10): 948-956. |
| [8] | 高薇1, 史伟1, 陈长会2, 文德年3, 田进2, 姚开虎1. 临床肺炎链球菌常见序列型青霉素耐药性的流行病学研究[J]. 遗传, 2016, 38(10): 940-947. |
| [9] | 张玉娇, 李晓静, 米凯霞. 结核分枝杆菌耐氟喹诺酮类药物的分子机制研究进展[J]. 遗传, 2016, 38(10): 918-927. |
| [10] | 王婷, 焦伟伟, 申阿东. 结核分枝杆菌乙胺丁醇耐药机制的研究进展[J]. 遗传, 2016, 38(10): 910-917. |
| [11] | 马丽娜, 米宏霏, 薛云新, 王岱, 赵西林. ROS在细菌耐药及抗生素杀菌中的作用机制[J]. 遗传, 2016, 38(10): 902-909. |
| [12] | 陈昱帆, 刘诗胤, 梁志彬, 吕明发, 周佳暖, 张炼辉. 群体感应与微生物耐药性[J]. 遗传, 2016, 38(10): 881-893. |
| [13] | 张刚, 冯婕. 细菌固有耐药的研究进展[J]. 遗传, 2016, 38(10): 872-880. |
| [14] | 谢龙祥, 于召箫, 郭思瑶, 李萍, AbualgasimElgailiAbdalla, 谢建平. 表观遗传和蛋白质翻译后修饰在细菌耐药中的作用[J]. 遗传, 2015, 37(8): 793-800. |
| [15] | 赵跃, 张宏, 夏雪山. 下一代半导体测序技术在遗传性心肌病分子诊断中的应用[J]. 遗传, 2015, 37(7): 635-644. |
| 阅读次数 | ||||||
|
全文 |
|
|||||
|
摘要 |
|
|||||
www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:
