Progress on the molecular mechanism of independent resistance and cross-resistance to isoniazid and prothionamide in Mycobacterium tuberculosis
WANG Xiao-ying1, ZHANG Hui-zheng2,LUO Ming2, ZENG Wan-ting3
1. Chongqing Medical and Pharmaceutical College, Chongqing 401331, China; 2. Chongqing Public Health Medical Center, Chongqing 400036, China; 3. People’s Liberation Army Special Medical Center, Daping Hospital,Chongqing 400042, China
Abstract:Tuberculosis is a respiratory infectious disease that threat to public health worldwide. According to the statistics of World Health Organization, the amount of multi-drug resistance tuberculosis patients was about 484 000 in the world during 2018. Isoniazid is an important first line anti-tuberculosis drug with seriously drug resistance at present. Prothionamide is an important second-line anti-tuberculosis drug, which can be used as replacement drug for isoniazid resistant patients. However, prothionamideis partially cross resistance to isoniazid, which will weaken the replaceable role of prothionamide. This paper reviewed the independent resistance and cross-resistance related genes of Mycobacterium tuberculosis to isoniazid and prothionamide, with an emphasis on cross-resistant related genes. At present, the gene mutation involved in isoniazid and prothionamide cross-resistance are mainly inhA, ndh and fabG1-inhA, with two of them (ndh and fabG1-inhA) are still controversial. The aim of this review is to provide reference for the treatment of isoniazid resistance and multi-drug resistance tuberculosis patients.
王晓英,张汇征,罗明,曾婉婷. 结核分枝杆菌异烟肼和丙硫异烟胺耐药及其交叉耐药相关机制研究进展[J]. 中国人兽共患病学报, 2020, 36(3): 234-238.
WANG Xiao-ying, ZHANG Hui-zheng,LUO Ming, ZENG Wan-ting. Progress on the molecular mechanism of independent resistance and cross-resistance to isoniazid and prothionamide in Mycobacterium tuberculosis. Chinese Journal of Zoonoses, 2020, 36(3): 234-238.
[1] Lawn SD, Zumla AI. Tuberculosis [J]. Lancet, 2011, 378(9785): 57-72. DOI: 10.1016/S0140-6736(10)62173-3 [2] WHO.Global Tuberculosis Report 2019 [EB/OL]. (2019-10-17)[2020-01-03]. Geneva: World Health Organization, 2019. http://www.who.int/tb/publications/global_report/en/ [3] 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[J]. 中国防痨杂志, 2012, 34(8): 485-508 [4] Winder FG. Mode of action of the antimycobacterial agents and associated aspects of the molecular biology of the mycobacteria[J]. Bio Mycobact, 1982, 1: 353-438 [5] 中国防痨协会. 耐药结核病化学治疗指南[J]. 中国防痨杂志, 2015, 37(5): 421-469. DOI: 10.3969/j.issn.1000-6621.2015.05.001 [6] Wang F, Langley R, Gulten G, et al. Mechanism of thioamide drug action against tuberculosis and leprosy [J]. J Exp Med, 2007, 204: 73-78. DOI: 10.1084/jem.20062100 [7] Thee S, Garcia-Prats AJ, Donald PR, et al. A review of the use of ethionamide and prothionamide in childhood tuberculosis[J]. Tuberculosis, 2016, 97: 126-136. DOI: 10.1016/j.tube.2015.09.007 [8] 肖和平, 唐神结. 二线抗结核药物的临床应用[J].中国防痨杂志, 2009,31(10):612-616 [9] Schaaf HS, Victor TC, Venter A, et al. Ethionamide cross-and co-resistance in children with isoniazid-resistant tuberculosis[J]. Int J Tuberc Lung Dis, 2009, 13(11): 1355-1359. DOI: 10.1258/ijsa.2009.009233 [10] Banerjee A, Dubnau E, Quemard A, et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis[J]. Science, 1994, 263:227-230. DOI:10.1126/science.8284673 [11] Vilcheze C, Jacobs WR Jr. Resistance to isoniazid and ethionamide in Mycobacterium tuberculosis: genes, mutations, and causalities [J]. Microbiol Spectr, 2014, 2:431-453. DOI: 10.1128/microbiolspec.MGM2-0014-2013 [12] Larsen MH, Vilchèze C, Kremer L, et al. Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. Tuberculosis [J]. Mol Microbiol,2002, 2: 453-466. DOI: 10.1046/j.1365-2958.2002.03162.x [13] Morlock GP, Metchock B, Sikes D, et al. ethA,inhA,and katG loci ofethionamide resistant clinical Mycobacterium tuberculosis isolates [J]. Antimicrob Agents Chemother, 2003, 47(12): 3799-3805. DOI: 10.1128/aac.47.12.3799-3805.2003 [14] Vilchèze C, Wang F, Arai M, et al. Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid [J].Nat Med, 2006, 12(9): 1027-1029. DOI:10.1038/nm1466 [15] Rueda J, Realpe T, Mejia GI, et al. Genotypic analysis of genes associated with independent resistance and cross-resistance to isoniazid and ethionamide in Mycobacterium tuberculosis clinical isolates [J]. Antimicrob Agents Chemother, 2015, 59:7805-7810. DOI:10.1128/AAC.01028-15 [16] Islam MM, Tan Y, Hameed HMA, et al. Detection of novel mutations associated with independent resistance and cross-resistance to isoniazid and prothionamide in Mycobacterium tuberculosis clinical isolates [J]. Clin Microbiol Infect, 2019, 25(8):1041.e1-1041.e7. DOI: 10.1016/j.cmi.2018.12.008 [17] Machado D, Perdigao J, Ramos J, et al. High-level resistance to isoniazid and ethionamide in multidrug-resistant Mycobacterium tuberculosis of the Lisboa family is associated with inhA double mutations[J].J Antimicrob Chemother, 2013, 68(8): 1728-32. DOI: 10.1093/jac/dkt090 [18] Rueda J, Realpe T, Mejia GI, et al. Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates[J]. Antimicrob Agents Chemotherapy, 2015, 59(12): 7805-7810. DOI: 10.1128/AAC.01028-15 [19] Muller B, Streicher EM, Hoek KG, et al. inhA promoter mutations: a gateway to extensively drug-resistant tuberculosis in South Africa [J]. Int J Tuberc Lung Dis, 2011, 15:344-351 [20] Hazbon MH, Brimacombe M, Bobadilla-del-Valle M, et al. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis[J]. Antimicrob Agents Chemother, 2006, 50(8): 2640-2649. DOI: 10.1128/AAC.00112-06 [21] Ristow M, Mohlig M, Rifai M, et al. New isoniazid/ethionamide resistance gene mutation and screening for multidrug-resistant Mycobacterium tuberculosis strains [J]. Lancet, 1995, 346: 502-503. DOI: 10.1016/s0140-6736(95)91351-3 [22] 陈杨,陈玲,张泓,等.耐异烟肼结核分枝杆菌及其katG与inhA基因突变的研究[J].中国抗生素杂志,2010,35(10):788-792 [23] 吴雪琼,钟敏,张俊仙,等.PCR直接测序法分析结核分枝杆菌katG基因突变[J].临床检验杂志,2000,18(1):9-11. DOI: 10.3969/j.issn.1001-764X.2000.01.014 [24] 朱中元,邵寒霜,陈允凤,等.结核分枝杆菌inhA基因突变的测序研究[J].中华结核和呼吸杂志,2001,24(1):48-51 [25] Boonaiam S, Chaiprasert A, Prammananan T, et al. Genotypic analysis of genes associated with isoniazid and ethionamide resistance in MDR-TB isolates from Thailand [J]. Clin Microbiol Infect, 2010, 16(4): 396-399. DOI: 10.1111/j.1469-0691.2009.02838.x [26] Lee H, Cho SN, Bang HE, et al. Exclusive mutations related to isoniazid and ethionamide resistance among Mycobacterium tuberculosis isolates from Korea [J]. Int J Tuberc Lung Dis, 2000, 4: 441-447 [27] Miesel L, Weisbrod TR, Marcinkeviciene JA, et al. NADH dehydrogenase defects confer isoniazid resistance and conditional lethality in Mycobacterium smegmatis [J]. J Bacteriol,1998, 180(9): 2459-2467 [28] Lee AS, Teo AS, Wong SY. Novel mutations in ndh in isoniazid-resistant Mycobacterium tuberculosis isolates[J]. Antimicrob Agents Chemother, 2001, 45: 2157-2159. DOI: 10.1128/AAC.45.7.2157-2159.2001 [29] Quemard A, Sacchettini JC, Dessen A, et al. Enzymatic characterization of the target for isoniazid in Mycobacterium tuberculosis[J]. Biochemistry, 1995, 34: 8235-8241. DOI: 10.1021/bi00026a004 [30] Rozwarski DA, Grant GA, Barton DH, et al. Modification of the NADH of the isoniazid target (inhA) from Mycobacterium tuberculosis[J]. Science, 1998, 279: 98-102. DOI: 10.1126/science.279.5347.98 [31] Brossier F, Veziris N, Truffot-Pernot C, et al. Molecular investigation of resistance to the antituberculous drug ethionamide in multidrug resistant clinical isolates of Mycobacterium tuberculosis[J]. Antimicrob Agents Chemother, 2011, 55: 355-360. DOI: 10.1128/AAC.01030-10 [32] Vilchèze C, Weisbrod TR, Chen B, et al. Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria[J]. Antimicrob Agents Chemother, 2005, 49: 708-720. DOI: 10.1128/AAC.49.2.708-720.2005 [33] Cardoso RF, Cardoso MA, Leite CQ, et al. Characterization of ndh gene of isoniazid resistant and susceptible Mycobacterium tuberculosis isolates from Brazil[J].Mem Inst Oswaldo Cruz, 2007, 102: 59-61. DOI: 10.1590/s0074-02762007000100009 [34] Ramaswamy SV, Reich R, Dou SJ, et al. Single nucleotide polymorphisms in genes associated with isoniazid resistance in Mycobacterium tuberculosis[J]. Antimicrob Agents Chemother, 2003, 47: 1241-1250. DOI: 10.1128/aac.47.4.1241-1250.2003 [35] Ando H, Miyoshi-Akiyama T, Watanabe S, et al. A silent mutation in mabA confers isoniazid resistance on Mycobacterium tuberculosis[J]. Mol Microbiol, 2014, 91(3): 538-547. DOI: 10.1111/mmi.12476 [36] Walker TM, Kohl TA, Omar SV, et al. Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study[J]. Lancet Infect Dis, 2015, 15: 1193-1202. DOI: 10.1016/S1473-3099(15)00062-6 [37] Tan Y, Su B, Zheng H, et al. Molecular Characterization of Prothionamide-Resistant Mycobacterium tuberculosis Isolates in Southern China[J]. Front Microbiol, 2017, 8:2358. DOI: 10.3389/fmicb.2017.02358 [38] Heym B, Zhang Y, Poulet S, et al. Characterization of the katG geneencoding a catalase-peroxidase required for the isoniazid susceptibility of Mycobacterium tuberculosis[J]. J Bacteriol, 1993, 175(13): 4255-4259. DOI: 10.1128/jb.175.13.4255-4259.1993 [39] Campbell PJ, Morlock GP, Sikes RD, et al. Molecular detection of mutations associated with first-and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis[J]. Antimicrob Agents Chemother, 2011, 55(5): 2032-2041. DOI: 10.1128/AAC.01550-10 [40] Mokrousov I, Narvskaya O, Otten T, et al. High prevalence of KatG Ser315Thr substitution among isoniazid-resistant Mycobacterium tuberculosis clinical isolates from northwestern Russia, 1996 to 2001[J]. Antimicrob Agents Chemother, 2002, 46: 1417-1424. DOI: 10.1128/aac.46.5.1417-1424.2002 [41] Bollela VR, Namburete EI, Feliciano CS, et al. Detection of katG and inhA mutations to guide isoniazid and ethionamide use fordrug-resistant tuberculosis [J]. Int J Tuberc Lung Dis, 2016, 20(8): 1099-1104. DOI: 10.5588/ijtld.15.0864 [42] Sherman DR, Mdluli K, Hickey MJ, et al. Compensatory ahpC gene expression in isoniazid-resistant Mycobacterium tuberculosis[J]. Science, 1996, 272: 1641-1643. DOI: 10.1126/science.272.5268.1641 [43] Sreevatsan S, Pan X, Zhang Y, et al. Analysis of the oxyR-ahpC region in isoniazid-resistant and-susceptible Mycobacterium tuberculosis complex organisms recovered from diseased humans and animals in diverse localities [J]. Anitimicrob Agents Chemother, 1997, 41(3):600-606 [44] Baker LV, Brown TJ, Maxwell O, et al. Molecular analysis of isoniazid-resistant Mycobacterium tuberculosis isolates from England and Wales reveals the phylogenetic significance of the ahpC-46A polymorphism [J]. Antimicrob Agents Chemother, 2005, 49: 1455-1464. DOI: 10.1128/AAC.49.4.1455-1464.2005 [45] Lee AS, Lim IH, Tang LL, et al. Contribution of kasA analysis to detection of isoniazid-resistant Mycobacterium tuberculosis in Singapore [J]. Antimicrob Agents Chemother, 1999, 43: 2087-2089.
[46] Zhang M, Yue J, Yang YP, et al. Detection of mutations associated with isoniazid resistance in Mycobacterium tuberculosis isolates from China [J]. J Clin Microbiol, 2005, 43: 5477-5482. DOI: 10.1128/JCM.43.11.5477-5482.2005 [47] Fraaije MW, Kamerbeek NM, Heidekamp AJ, et al. The prodrug activator EtaA from Mycobacterium tuberculosis is a Baeyer-Villiger monooxygenase[J]. J Biol Chem, 2004, 279(5): 3354-3360. DOI: 10.1074/jbc.M307770200 [48] Vannelli TA, Dykman A, Ortiz De Montellano PR, et al. The antituberculosis drug ethionamide is activated by a flavoprotein monooxygenase[J]. J Biol Chem, 2002, 277(15): 12824-12829. DOI: 10.1074/jbc.M110751200 [49] Baulard AR, Betts JC, Engohang-Ndong J, et al. Activation of the pro-drug ethionamide is regulated in mycobacteria[J]. J Biol Chem, 2000, 275(36): 28326-28331. DOI: 10.1074/jbc.M003744200 [50] Debarber AE, Mdluli K, Bosman M, et al. Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis[J]. Proc Natl Acad Sci USA, 2000, 97(17): 9677-9682. DOI: 10.1073/pnas.97.17.9677 [51] Casali N, Nikolayevskyy V, Balabanova Y, et al. Evolution and transmission of drug-resistant tuberculosis in a Russian population[J]. Nat Genet, 2014, 46: 279-286. DOI: 10.1038/ng.2878 [52] Engohang-Ndong J, Baillat D, Aumercier M, et al. EthR, a repressor of the TetR/CamR family implicated in ethionamideresistance in mycobacteria, octamerizes cooperatively on its operator[J]. Mol Microbiol, 2004, 51: 175-188. DOI: 10.1046/j.1365-2958.2003.03809.x