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结核分枝杆菌耐药机制的研究进展
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Abstract:
结核病(Tuberculosis, TB)是由结核分枝杆菌(Mycobacterium tuberculosis, MTB)引发的慢性传染病，不仅有极高的致死性，更是全球公共卫生领域所面临的巨大挑战。而耐药结核的出现更是给这一挑战雪上加霜。耐药结核是指患者体内的MTB在进化的过程中，躲避宿主的免疫监控，进而降低抗结核药物效力。这一现象的背后，与抗生素的滥用、抗结核药物的不规范使用以及MTB自身的演变等因素紧密相连。面对这一严峻的现实，对MTB的耐药机制进行深入的研究不仅有助于我们更好地理解这一疾病的本质，更能为后续的快速分子诊断工具的开发以及新型抗结核药物的研发提供参考。
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB). It is not only extremely lethal, but also a huge challenge facing the global public health field. The emergence of drug-resistant tuberculosis has made this challenge even worse. Drug-resistant tuberculosis (TB) refers to the continuous evolution of MTB in the patient’s body, which makes it evade the immune surveillance of the host, reduces the efficacy of anti-tuberculosis drugs. Antibiotic abuse, non-standard use of anti-tuberculosis drugs, and the evolution of MTB itself are all causes of MTB resistance. Faced with this grim reality, in depth research on the drug resistance mechanism of MTB will not only help us better understand the nature of this disease, but also provide a reference for the subsequent development of rapid molecular diagnostic tools and the research and development of new anti-tuberculosis drugs.
| [1] | World Health Organization (2022) Global Tuberculosis Report 2022. Geneva. |
| [2] | 郑伟, 田甜, 王琦, 等. 结核分枝杆菌的耐药机制研究进展[J]. 中国人兽共患病学报, 2021, 37(11): 1044-1052. |
| [3] | Batt, S.M., Burke, C.E., Moorey, A.R. and Besra, G.S. (2020) Antibiotics and Resistance: The Two-Sided Coin of the Mycobacterial Cell Wall. The Cell Surface, 6, Article ID: 100044. https://doi.org/10.1016/j.tcsw.2020.100044 |
| [4] | Shaku, M.T., Ocius, K.L., Apostolos, A.J., Pires, M.M., Van Nieuwenhze, M.S., Dhar, N., et al. (2023) Amidation of Glutamate Residues in Mycobacterial Peptidoglycan Is Essential for Cell Wall Cross-Linking. Frontiers in Cellular and Infection Microbiology, 13, Article 1205829. https://doi.org/10.3389/fcimb.2023.1205829 |
| [5] | Ballister, E.R., Samanovic, M.I. and Darwin, K.H. (2019) Mycobacterium Tuberculosis Rv2700 Contributes to Cell Envelope Integrity and Virulence. Journal of Bacteriology, 201, e00228-19. https://doi.org/10.1128/jb.00228-19 |
| [6] | Capela, R., Félix, R., Clariano, M., Nunes, D., Perry, M.D.J. and Lopes, F. (2023) Target Identification in Anti-Tuberculosis Drug Discovery. International Journal of Molecular Sciences, 24, Article 10482. https://doi.org/10.3390/ijms241310482 |
| [7] | Kanji, A., Hasan, R. and Hasan, Z. (2019) Efflux Pump as Alternate Mechanism for Drug Resistance in Mycobacterium Tuberculosis. Indian Journal of Tuberculosis, 66, 20-25. https://doi.org/10.1016/j.ijtb.2018.07.008 |
| [8] | Hasan, Z., Razzak, S.A., Kanji, A., Shakoor, S. and Hasan, R. (2024) Efflux Pump Gene Single Nucleotide Variants Associated with Resistance in Mycobacterium Tuberculosis Isolates with Discrepant Drug Genotypes. Journal of Global Antimicrobial Resistance. https://doi.org/10.1016/j.jgar.2024.05.006 |
| [9] | Meikle, V., Zhang, L. and Niederweis, M. (2023) Intricate Link between Siderophore Secretion and Drug Efflux in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 67, e01629-22. https://doi.org/10.1128/aac.01629-22 |
| [10] | Antil, M. and Gupta, V. (2022) Lessons Learnt and the Way Forward for Drug Development against Isocitrate Lyase from Mycobacterium tuberculosis. Protein & Peptide Letters, 29, 1031-1041. https://doi.org/10.2174/0929866529666221006121831 |
| [11] | Limón, G., Samhadaneh, N.M., Pironti, A. and Darwin, K.H. (2023) Aldehyde Accumulation in Mycobacterium tuberculosis with Defective Proteasomal Degradation Results in Copper Sensitivity. mBio, 2023, e00363-23. https://doi.org/10.1128/mbio.00363-23 |
| [12] | Vilchèze, C. and Jacobs Jr., W.R. (2014) Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities. Microbiology Spectrum, 2, MGM2-0014-2013. |
| [13] | Reta, M.A., Alemnew, B., Abate, B.B. and Fourie, P.B. (2021) Prevalence of Drug Resistance-Conferring Mutations Associated with Isoniazid-and Rifampicin-Resistant Mycobacterium Tuberculosis in Ethiopia: A Systematic Review and Meta-Analysis. Journal of Global Antimicrobial Resistance, 26, 207-218. https://doi.org/10.1016/j.jgar.2021.06.009 |
| [14] | Valafar, S.J. (2021) Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium Tuberculosis. Antimicrobial Agents and Chemotherapy, 65, e02091-20. https://doi.org/10.1128/aac.02091-20 |
| [15] | Norouzi, F., Moghim, S., Farzaneh, S., Fazeli, H., Salehi, M. and Nasr Esfahani, B. (2021) Significance of the Coexistence of Non-Codon 315 katG, inhA, and oxyR-ahpC Intergenic Gene Mutations among Isoniazid-Resistant and Multidrug-Resistant Isolates of Mycobacterium Tuberculosis: A Report of Novel Mutations. Pathogens and Global Health, 116, 22-29. https://doi.org/10.1080/20477724.2021.1928870 |
| [16] | Bakhtiyariniya, P., Khosravi, A.D., Hashemzadeh, M. and Savari, M. (2022) Detection and Characterization of Mutations in Genes Related to Isoniazid Resistance in Mycobacterium Tuberculosis Clinical Isolates from Iran. Molecular Biology Reports, 49, 6135-6143. https://doi.org/10.1007/s11033-022-07404-2 |
| [17] | Zarei, Z., Emami, A., Moghadami, M., Kashkooli, G.S. and Pirbonyeh, N. (2017) Molecular Characterization of Isoniazid and Rifampicin Target Genes in Multi-Drug Resistant Mycobacterium Tuberculosis Isolates from Southwest of Iran. Gene Reports, 6, 19-25. https://doi.org/10.1016/j.genrep.2016.11.003 |
| [18] | 司晓燕, 陈俊林, 施慧慧, 等. 体外诱导获取利福平耐药结核分枝杆菌菌株及其稳定性研究[J]. 交通医学, 2022, 36(1): 10-14, 18. https://doi.org/10.19767/j.cnki.32-1412.2022.01.003 |
| [19] | Barliana, M.I., Afifah, N.N., Yunivita, V. and Ruslami, R. (2023) Genetic Polymorphism Related to Ethambutol Outcomes and Susceptibility to Toxicity. Frontiers in Genetics, 14, Article 1118102. https://doi.org/10.3389/fgene.2023.1118102 |
| [20] | Xiang, X., Gong, Z., Deng, W., Sun, Q. and Xie, J. (2020) Mycobacterial Ethambutol Responsive Genes and Implications in Antibiotics Resistance. Journal of Drug Targeting, 29, 284-293. https://doi.org/10.1080/1061186x.2020.1853733 |
| [21] | Tulyaprawat, O., Chaiprasert, A., Chongtrakool, P., Suwannakarn, K. and Ngamskulrungroj, P. (2019) Association of Ubia Mutations and High-Level of Ethambutol Resistance among Mycobacterium Tuberculosis Thai Clinical Isolates. Tuberculosis, 114, 42-46. https://doi.org/10.1016/j.tube.2018.11.006 |
| [22] | Sun, Q., Zou, Y., Feng, Q., Gong, Z., Song, M., Li, M., et al. (2023) The Acetylation of pknH Is Linked to the Ethambutol Resistance of Mycobacterium Tuberculosis. Archives of Microbiology, 205, Article No. 337. https://doi.org/10.1007/s00203-023-03676-9 |
| [23] | Lingaraju, S., Rigouts, L., Gupta, A., Lee, J., Umubyeyi, A.N., Davidow, A.L., et al. (2016) Geographic Differences in the Contribution of ubiA Mutations to High-Level Ethambutol Resistance in Mycobacterium Tuberculosis. Antimicrobial Agents and Chemotherapy, 60, 4101-4105. https://doi.org/10.1128/aac.03002-15 |
| [24] | ？zgür, D., Kayar, M.B., Bi？men, C., et al. (2017) Investigation of pncA, rpsA and panD Gene Mutations Associated with Resistance in Pyrazinamide-Resistant Mycobacterium Tubercresistance-Associated Mutations in Clinical Isolates: PncA Mutations and PZA Resistance in M. tuberculosis in Vietnam. Emerging Microbes & Infections, 6, 1-7. |
| [25] | Rajendran, A. and Palaniyandi, K. (2022) Mutations Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis: A Review and Update. Current Microbiology, 79, Article No. 348. https://doi.org/10.1007/s00284-022-03032-y |
| [26] | Shahab, M., de Farias Morais, G.C., Akash, S., Fulco, U.L., Oliveira, J.I.N., Zheng, G., et al. (2024) A Robust Computational Quest: Discovering Potential Hits to Improve the Treatment of Pyrazinamide-Resistant Mycobacterium tuberculosis. Journal of Cellular and Molecular Medicine, 28, e18279. https://doi.org/10.1111/jcmm.18279 |
| [27] | Wang, Y., Li, Q., Gao, H., et al. (2019) The Roles of rpsL, rrs, and gidB Mutations in Predicting Streptomycin-Resistant Drugs Used on Clinical Mycobacterium tuberculosis Isolates from Hebei Province, China. International Journal of Clinical and Experimental Pathology, 12, 2713. |
| [28] | Rocha, D.M.G.C., Viveiros, M., Saraiva, M. and Osório, N.S. (2021) The Neglected Contribution of Streptomycin to the Tuberculosis Drug Resistance Problem. Genes, 12, Article 2003. https://doi.org/10.3390/genes12122003 |
| [29] | Al-Mutairi, N.M., Ahmad, S. and Mokaddas, E. (2024) Discordance in Phenotypic and Genotypic Susceptibility Testing for Streptomycin Due to Nonsynonymous/Nonsense/Deletion Frame-Shift Mutations in gidB among Clinical Mycobacterium tuberculosis Isolates in Kuwait. Medical Principles and Practice. https://doi.org/10.1159/000538584 |
| [30] | Vīksna, A., Sadovska, D., Berge, I., Bogdanova, I., Vaivode, A., Freimane, L., et al. (2023) Genotypic and Phenotypic Comparison of Drug Resistance Profiles of Clinical Multidrug-Resistant Mycobacterium tuberculosis Isolates Using Whole Genome Sequencing in Latvia. BMC Infectious Diseases, 23, Article No. 638. https://doi.org/10.1186/s12879-023-08629-7 |
| [31] | Liu, Y.Y., Shi, J., Chu, P., et al. (2022) Exploratory Study on Detection of Drug Resistance of Mycobacterium tuberculosis in Sputum Specimens by Next-Generation Sequencing. Chinese Journal of Tuberculosis and Respiratory Diseases, 45, 552-559. |
| [32] | Rueda, J., Realpe, T., Mejia, G.I., Zapata, E., Rozo, J.C., Ferro, B.E., et al. (2015) Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates. Antimicrobial Agents and Chemotherapy, 59, 7805-7810. https://doi.org/10.1128/aac.01028-15 |
| [33] | Mugumbate, G., Mendes, V., Blaszczyk, M., Sabbah, M., Papadatos, G., Lelievre, J., et al. (2017) Target Identification of Mycobacterium Tuberculosis Phenotypic Hits Using a Concerted Chemogenomic, Biophysical, and Structural Approach. Frontiers in Pharmacology, 8, Article 681. https://doi.org/10.3389/fphar.2017.00681 |
| [34] | Gries, R., Chhen, J., van Gumpel, E., Theobald, S.J., Sonnenkalb, L., Utpatel, C., et al. (2024) Discovery of Dual-Active Ethionamide Boosters Inhibiting the Mycobacterium Tuberculosis ESX-1 Secretion System. Cell Chemical Biology, 31, 699-711.E6. https://doi.org/10.1016/j.chembiol.2023.12.007 |
| [35] | Zhang, X., Chen, X., Wang, B., Fu, L., Huo, F., Gao, T., et al. (2021) Molecular Characteristic of Both Levofloxacin and Moxifloxacin Resistance in Mycobacterium tuberculosis from Individuals Diagnosed with Preextensive Drug-Resistant Tuberculosis. Microbial Drug Resistance, 28, 280-287. https://doi.org/10.1089/mdr.2021.0212 |
| [36] | Chawla, K., Kumar, A., Shenoy, V.P., Chakrabarty, S. and Satyamoorthy, K. (2018) Genotypic Detection of Fluoroquinolone Resistance in Drug-Resistant Mycobacterium Tuberculosis at a Tertiary Care Centre in South Coastal Karnataka, India. Journal of Global Antimicrobial Resistance, 13, 250-253. https://doi.org/10.1016/j.jgar.2018.01.023 |
| [37] | Chong, Y., Li, X., Long, Y., Pei, S., Ren, Q., Feng, F., et al. (2024) Identification of Novel Resistance-Associated Mutations and Discrimination within Whole-Genome Sequences of Fluoroquinolone-Resistant Mycobacterium tuberculosis Isolates. Microbiology Spectrum, 12, e03930-23. https://doi.org/10.1128/spectrum.03930-23 |
| [38] | Wei, W., Yan, H., Zhao, J., Li, H., Li, Z., Guo, H., et al. (2019) Multi-Omics Comparisons of p-Aminosalicylic Acid (PAS) Resistance in folC Mutated and Un-Mutated Mycobacterium tuberculosis Strains. Emerging Microbes & Infections, 8, 248-261. https://doi.org/10.1080/22221751.2019.1568179 |
| [39] | 葛赛, 孙曼銮, 李昭阳. 翻译后修饰对结核分枝杆菌耐药性调控机制的研究[J]. 中国人兽共患病学报, 2023, 39(5): 500-508. |
| [40] | Zhang, Y., Wang, S., Chen, X., et al. (2024) Mutations in the Promoter Region of Methionine Transporter Gene metM (Rv3253c) Confer Para-Aminosalicylic Acid (PAS) Resistance in Mycobacterium tuberculosis. mBio, 15, e02073-23. |
| [41] | Kumar, R., Singh, N., Chauhan, A., Kumar, M., Bhatta, R.S. and Singh, S.K. (2022) Mycobacterium Tuberculosis Survival and Biofilm Formation Studies: Effect of D-Amino Acids, D-Cycloserine and Its Components. The Journal of Antibiotics, 75, 472-479. https://doi.org/10.1038/s41429-022-00534-6 |
| [42] | Osorio-González, A., álvarez, N., Realpe, T. and Robledo, J. (2024) Protocol for the Selection of Mycobacterium tuberculosis Spontaneous Resistant Mutants to D-Cycloserine. MethodsX, 12, Article ID: 102690. https://doi.org/10.1016/j.mex.2024.102690 |
| [43] | Yao, C., Guo, H., Li, Q., Zhang, X., Shang, Y., Li, T., et al. (2021) Prevalence of Extensively Drug-Resistant Tuberculosis in a Chinese Multidrug-Resistant TB Cohort after Redefinition. Antimicrobial Resistance & Infection Control, 10, Article No. 126. https://doi.org/10.1186/s13756-021-00995-8 |
| [44] | Rodrigues, C., Nambiar, R., Tornheim, J., Diricks, M., De Bruyne, K., Sadani, M., et al. (2021) Linezolid Resistance in Mycobacterium Tuberculosis Isolates at a Tertiary Care Centre in Mumbai, India. Indian Journal of Medical Research, 154, 85-89. https://doi.org/10.4103/ijmr.ijmr_1168_19 |
| [45] | Islam, M.M., Alam, M.S., Liu, Z., Khatun, M.S., Yusuf, B., Hameed, H.M.A., et al. (2024) Molecular Mechanisms of Resistance and Treatment Efficacy of Clofazimine and Bedaquiline against Mycobacterium tuberculosis. Frontiers in Medicine, 10, Article 1304857. https://doi.org/10.3389/fmed.2023.1304857 |
| [46] | Divita, K.M. and Khatik, G.L. (2021) Current Perspective of ATP Synthase Inhibitors in the Management of the Tuberculosis. Current Topics in Medicinal Chemistry, 21, 1623-1643. https://doi.org/10.2174/1568026621666210913122346 |
| [47] | Gómez-González, P.J., Perdigao, J., Gomes, P., Puyen, Z.M., Santos-Lazaro, D., Napier, G., et al. (2021) Genetic Diversity of Candidate Loci Linked to Mycobacterium Tuberculosis Resistance to Bedaquiline, Delamanid and Pretomanid. Scientific Reports, 11, Article No. 19431. https://doi.org/10.1038/s41598-021-98862-4 |
| [48] | Ge, Y., Luo, Q., Liu, L., Shi, Q., Zhang, Z., Yue, X., et al. (2024) S288T Mutation Altering Mmpl3 Periplasmic Domain Channel and H-Bond Network: A Novel Dual Drug Resistance Mechanism. Journal of Molecular Modeling, 30, Article No. 39. https://doi.org/10.1007/s00894-023-05814-y |
