Harnessing Bioinformatics to Decode Drug Resistance and Guide Vaccine Design in Mycobacterium tuberculosis
DOI:
https://doi.org/10.70411/MJHAS.3.2.2026401الكلمات المفتاحية:
Bioinformatics، Drug resistance، Epitope-based vaccine design، Tuberculosis genomicsالملخص
Mycobacterium tuberculosis presents a major challenge to global health due to tuberculosis (TB), which is worsened by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. This study provides a thorough examination of bioinformatics research, highlighting how the integration of genomic, proteomic and metabolomic data into TB research has revolutionised the way TB is studied, particularly in understanding resistance mechanisms, identifying new therapeutic targets, and expediting the development of diagnostic tools and vaccines. Whole-genome sequencing (WGS) and newer technologies like Oxford Nanopore Technologies (ONT) have since paved the way to the rapid identification of strain-specific mutations, with novel bioinformatics tools like PhyResSE, Mykrobe and GBOOST offering a powerful platform in mutation profiling, resistance prediction and strain classification. Furthermore, resistance prediction is also being transformed by machine learning and AI-based models, which improve the accuracy of clinical choices and monitoring options. Epitope prediction, molecular docking, and analysis of population coverage to inform the selection of promising immunogenic candidates are also proposed in the study as an in silico pipeline of rational vaccine design. Although continued efforts at infrastructure, standardisation, and workforce training are always ongoing in many settings where this is still seen as a major issue, especially in high-burden settings, this paradigm shift in an interdisciplinary approach is a clear indication of progress in the fight against one of the most prevalent and persistent infectious diseases in the world.
المراجع
Acharya, B., Acharya, A., Gautam, S., Ghimire, S. P., Mishra, G., Parajuli, N., & Sapkota, B. (2020). Advances in diagnosis of Tuberculosis: An update into molecular diagnosis of Mycobacterium tuberculosis. Molecular Biology Reports, 47(5), 4065–4075. https://doi.org/10.1007/s11033-020-05413-7
Alaridah, N., Hallbäck, E. T., Tångrot, J., Winqvist, N., Sturegård, E., Florén-Johansson, K., Jönsson, B., Tenland, E., Welinder-Olsson, C., Medstrand, P., Kaijser, B., & Godaly, G. (2019). Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden. Scientific Reports, 9(1), 4931. https://doi.org/10.1038/s41598-019-39971-z
Bakuła, Z., Dziurzyński, M., Decewicz, P., Bakonytė, D., Vasiliauskaitė, L., Nakčerienė, B., Krenke, R., Stakėnas, P., & Jagielski, T. (2023). Spoligotyping of Mycobacterium tuberculosis – Comparing in vitro and in silico approaches. Infection, Genetics and Evolution, 115, 105508. https://doi.org/10.1016/j.meegid.2023.105508
Bakuła, Z., Marczak, M., Bluszcz, A., Proboszcz, M., Kościuch, J., Krenke, R., Stakėnas, P., Mokrousov, I., & Jagielski, T. (2023). Phylogenetic relationships of Mycobacterium tuberculosis isolates in Poland: The emergence of Beijing genotype among multidrug-resistant cases. Frontiers in Cellular and Infection Microbiology, 13, 1161905. https://doi.org/10.3389/fcimb.2023.1161905
Bellad, R., Nagamoti, M., Sharma, P., & Chauhan, D. S. (2022). Spoligotyping of Mycobacterium tuberculosis isolates from Pulmonary Tuberculosis patients from North Karnataka, India. Tropical Doctor, 52(3), 386–390. https://doi.org/10.1177/00494755221080584
Bogaerts, B., Delcourt, T., Soetaert, K., Boarbi, S., Ceyssens, P.-J., Winand, R., Van Braekel, J., De Keersmaecker, S. C. J., Roosens, N. H. C., Marchal, K., Mathys, V., & Vanneste, K. (2021). A Bioinformatics Whole-Genome Sequencing Workflow for Clinical Mycobacterium tuberculosis Complex Isolate Analysis, Validated Using a Reference Collection Extensively Characterized with Conventional Methods and In Silico Approaches. Journal of Clinical Microbiology, 59(6), e00202-21. https://doi.org/10.1128/JCM.00202-21
Cancino-Muñoz, I., López, M. G., Torres-Puente, M., Villamayor, L. M., Borrás, R., Borrás-Máñez, M., Bosque, M., Camarena, J. J., Colijn, C., Colomer-Roig, E., Colomina, J., Escribano, I., Esparcia-Rodríguez, O., García-García, F., Gil-Brusola, A., Gimeno, C., Gimeno-Gascón, A., Gomila-Sard, B., Gónzales-Granda, D., … Comas, I. (2022). Population-based sequencing of Mycobacterium tuberculosis reveals how current population dynamics are shaped by past epidemics. eLife, 11, e76605. https://doi.org/10.7554/eLife.76605
Chen, J., Chen, L., Zhou, M., Wu, G., Yi, F., Jiang, C., Duan, Q., & Zhou, M. (2022). Transmission of multidrug-resistant tuberculosis within family households by DTM-PCR and MIRU-VNTR genotyping. BMC Infectious Diseases, 22(1), 192. https://doi.org/10.1186/s12879-022-07188-7
Chesov, E., Chesov, D., Maurer, F. P., Andres, S., Utpatel, C., Barilar, I., Donica, A., Reimann, M., Niemann, S., Lange, C., Crudu, V., Heyckendorf, J., & Merker, M. (2022). Emergence of bedaquiline resistance in a high tuberculosis burden country. European Respiratory Journal, 59(3), 2100621. https://doi.org/10.1183/13993003.00621-2021
Chisompola, N. K., Streicher, E. M., Dippenaar, A., Whitfield, M. G., Tembo, M., Mwanza, S., Warren, R. M., & Sampson, S. L. (2021). Drug resistant tuberculosis cases from the Copperbelt province and Northern regions of Zambia: Genetic diversity, demographic and clinical characteristics. Tuberculosis, 130, 102122. https://doi.org/10.1016/j.tube.2021.102122
Couvin, D., Allaguy, A.-S., Ez-zari, A., Jagielski, T., & Rastogi, N. (2025). Molecular typing of Mycobacterium tuberculosis: A review of current methods, databases, softwares, and analytical tools. FEMS Microbiology Reviews, 49, fuaf017. https://doi.org/10.1093/femsre/fuaf017
Couvin, D., Segretier, W., Stattner, E., & Rastogi, N. (2020). Novel methods included in SpolLineages tool for fast and precise prediction of Mycobacterium tuberculosis complex spoligotype families. Database, 2020, baaa108. https://doi.org/10.1093/database/baaa108
Dawood, A. A. (2024). Designing an immuno-epitope candidate vaccine from (Opa, ProA, ProB, RmpM and BamD) proteins against Neisseria gonorrhoeae and Neisseria meningitides. Vacunas (English Edition), 25(4), 481–491. https://doi.org/10.1016/j.vacune.2024.10.009
Dawood, A., & Alnori, H. A.-M. (2020). Tunicamycin Anticancer Drug May Reliable to Treat Coronavirus Disease-19. Open Access Macedonian Journal of Medical Sciences, 8(T1), 129–133. https://doi.org/10.3889/oamjms.2020.4954
Gautam, S. S., Mac Aogáin, M., Cooley, L. A., Haug, G., Fyfe, J. A., Globan, M., & O’Toole, R. F. (2018). Molecular epidemiology of tuberculosis in Tasmania and genomic characterisation of its first known multi-drug resistant case. PLOS ONE, 13(2), e0192351. https://doi.org/10.1371/journal.pone.0192351
Genestet, C., Hodille, E., Bernard, A., Vallée, M., Lina, G., Le Meur, A., Refrégier, G., & Dumitrescua, O. (2022). Consistency of Mycobacterium tuberculosis Complex Spoligotyping between the Membrane-Based Method and In Silico Approach. Microbiology Spectrum, 10(3), e00223-22. https://doi.org/10.1128/spectrum.00223-22
Guyeux, C., Senelle, G., Le Meur, A., Supply, P., Gaudin, C., Phelan, J. E., Clark, T. G., Rigouts, L., De Jong, B., Sola, C., & Refrégier, G. (2024). Newly Identified Mycobacterium africanum Lineage 10, Central Africa. Emerging Infectious Diseases, 30(3). https://doi.org/10.3201/eid3003.231466
Guyeux, C., Sola, C., Noûs, C., & Refrégier, G. (2021). CRISPRbuilder-TB: “CRISPR-builder for tuberculosis”. Exhaustive reconstruction of the CRISPR locus in mycobacterium tuberculosis complex using SRA. PLOS Computational Biology, 17(3), e1008500. https://doi.org/10.1371/journal.pcbi.1008500
Haft, D. H., Badretdin, A., Coulouris, G., DiCuccio, M., Durkin, A. S., Jovenitti, E., Li, W., Mersha, M., O’Neill, K. R., Virothaisakun, J., & Thibaud-Nissen, F. (2024). RefSeq and the prokaryotic genome annotation pipeline in the age of metagenomes. Nucleic Acids Research, 52(D1), D762–D769. https://doi.org/10.1093/nar/gkad988
Hatherell, H.-A., Colijn, C., Stagg, H. R., Jackson, C., Winter, J. R., & Abubakar, I. (2016). Interpreting whole genome sequencing for investigating tuberculosis transmission: A systematic review. BMC Medicine, 14(1), 21. https://doi.org/10.1186/s12916-016-0566-x
He, G., Li, Y., Chen, X., Chen, J., & Zhang, W. (2020). Prediction of treatment outcomes for multidrug-resistant tuberculosis by whole-genome sequencing. International Journal of Infectious Diseases, 96, 68–72. https://doi.org/10.1016/j.ijid.2020.04.043
Hussien, B., Zewude, A., Wondale, B., Hailu, A., & Ameni, G. (2022). Spoligotyping of Clinical Isolates of Mycobacterium tuberculosis Complex Species in the Oromia Region of Ethiopia. Frontiers in Public Health, 10, 808626. https://doi.org/10.3389/fpubh.2022.808626
Jajou, R., Kohl, T. A., Walker, T., Norman, A., Cirillo, D. M., Tagliani, E., Niemann, S., De Neeling, A., Lillebaek, T., Anthony, R. M., & Van Soolingen, D. (2019). Towards standardisation: Comparison of five whole genome sequencing (WGS) analysis pipelines for detection of epidemiologically linked tuberculosis cases. Eurosurveillance, 24(50). https://doi.org/10.2807/1560-7917.ES.2019.24.50.1900130
Kargarpour Kamakoli, M., Farmanfarmaei, G., Masoumi, M., Khanipour, S., Gharibzadeh, S., Sola, C., Fateh, A., Siadat, S. D., Refregier, G., & Vaziri, F. (2020). Prediction of the hidden genotype of mixed infection strains in Iranian tuberculosis patients. International Journal of Infectious Diseases, 95, 22–27. https://doi.org/10.1016/j.ijid.2020.03.056
Katale, B. Z., Mbelele, P. M., Lema, N. A., Campino, S., Mshana, S. E., Rweyemamu, M. M., Phelan, J. E., Keyyu, J. D., Majigo, M., Mbugi, E. V., Dockrell, H. M., Clark, T. G., Matee, M. I., & Mpagama, S. (2020). Whole genome sequencing of Mycobacterium tuberculosis isolates and clinical outcomes of patients treated for multidrug-resistant tuberculosis in Tanzania. BMC Genomics, 21(1), 174. https://doi.org/10.1186/s12864-020-6577-1
Kohl, T. A., Utpatel, C., Schleusener, V., De Filippo, M. R., Beckert, P., Cirillo, D. M., & Niemann, S. (2018). MTBseq: A comprehensive pipeline for whole genome sequence analysis of Mycobacterium tuberculosis complex isolates. PeerJ, 6, e5895. https://doi.org/10.7717/peerj.5895
Lam, C., Martinez, E., Crighton, T., Furlong, C., Donnan, E., Marais, B. J., & Sintchenko, V. (2021). Value of routine whole genome sequencing for Mycobacterium tuberculosis drug resistance detection. International Journal of Infectious Diseases, 113, S48–S54. https://doi.org/10.1016/j.ijid.2021.03.033
Leong, K. W. C., Gautam, S. S., Pradhan, M., Singh, Y. I., Kc, R., Rajbhandari, S. K., Ghimire, G. R., Adhikari, K., Shrestha, U., Chaudhary, R., Ghimire, G., Khadka, S., & O’Toole, R. F. (2022). Comparative genomic analyses of multi-drug resistant Mycobacterium tuberculosis from Nepal and other geographical locations. Genomics, 114(2), 110278. https://doi.org/10.1016/j.ygeno.2022.110278
Mekonnen, D., Munshea, A., Nibret, E., Adnew, B., Herrera-Leon, S., Amor Aramendia, A., Benito, A., Abascal, E., Jacqueline, C., Aseffa, A., & Herrera-Leon, L. (2023). Comparative whole-genome sequence analysis of Mycobacterium tuberculosis isolated from pulmonary tuberculosis and tuberculous lymphadenitis patients in Northwest Ethiopia. Frontiers in Microbiology, 14, 1211267. https://doi.org/10.3389/fmicb.2023.1211267
Moco, V., Cazenave, D., Garnier, M., Pot, M., Marcelino, I., Talarmin, A., Guyomard-Rabenirina, S., Breurec, S., Ferdinand, S., Dereeper, A., Reynaud, Y., & Couvin, D. (2022). getSequenceInfo: A suite of tools allowing to get genome sequence information from public repositories. BMC Bioinformatics, 23(1), 268. https://doi.org/10.1186/s12859-022-04809-5
Morey-León, G., Mejía-Ponce, P. M., Granda Pardo, J. C., Muñoz-Mawyin, K., Fernández-Cadena, J. C., García-Moreira, E., Andrade-Molina, D., Licona-Cassani, C., & Berná, L. (2023). A precision overview of genomic resistance screening in Ecuadorian isolates of Mycobacterium tuberculosis using web-based bioinformatics tools. PLOS ONE, 18(12), e0294670. https://doi.org/10.1371/journal.pone.0294670
Puustinen, K., Marjamäki, M., Rastogi, N., Sola, C., Filliol, I., Ruutu, P., Holmström, P., Viljanen, M. K., & Soini, H. (2003). Characterization of Finnish Mycobacterium tuberculosis Isolates by Spoligotyping. Journal of Clinical Microbiology, 41(4), 1525–1528. https://doi.org/10.1128/JCM.41.4.1525-1528.2003
Rosenthal, A., Gabrielian, A., Engle, E., Hurt, D. E., Alexandru, S., Crudu, V., Sergueev, E., Kirichenko, V., Lapitskii, V., Snezhko, E., Kovalev, V., Astrovko, A., Skrahina, A., Taaffe, J., Harris, M., Long, A., Wollenberg, K., Akhundova, I., Ismayilova, S., … Tartakovsky, M. (2017). The TB Portals: An Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis. Journal of Clinical Microbiology, 55(11), 3267–3282. https://doi.org/10.1128/JCM.01013-17
Sola, C., Filliol, I., Gutierrez, M. C., Mokrousov, I., Vincent, V., & Rastogi, N. (2001). Spoligotype Database of Mycobacterium tuberculosis: Biogeographic Distribution of Shared Types and Epidemiologic and Phylogenetic Perspectives. Emerging Infectious Diseases, 7(3), 390–396. https://doi.org/10.3201/eid0703.010304
Tafaj, S., Ghariani, A., Trovato, A., Kapisyzi, P., Essalah, L., Mehiri, E., Kasmi, G., Burazeri, G., Slim Saidi, L., & Cirillo, D. M. (2020). Accuracy of the QIAxcel Automated System for MIRU-VNTR Genotyping of Mycobacterium tuberculosis in Two Limited Resource Settings. Journal of Clinical Medicine, 9(2), 389. https://doi.org/10.3390/jcm9020389
Yin, C., Mijiti, X., Liu, H., Wang, Q., Cao, B., Anwaierjiang, A., Li, M., Liu, M., Jiang, Y., Xu, M., Wan, K., Zhao, X., Li, G., & Xiao, H. (2023a). Molecular Epidemiology of Clinical Mycobacterium tuberculosis Isolates from Southern Xinjiang, China Using Spoligotyping and 15-Locus MIRU-VNTR Typing. Infection and Drug Resistance, Volume 16, 1313–1326. https://doi.org/10.2147/IDR.S393192
Yin, C., Mijiti, X., Liu, H., Wang, Q., Cao, B., Anwaierjiang, A., Li, M., Liu, M., Jiang, Y., Xu, M., Wan, K., Zhao, X., Li, G., & Xiao, H. (2023b). Molecular Epidemiology of Clinical Mycobacterium tuberculosis Isolates from Southern Xinjiang, China Using Spoligotyping and 15-Locus MIRU-VNTR Typing. Infection and Drug Resistance, Volume 16, 1313–1326. https://doi.org/10.2147/IDR.S393192
Zhang, X., Martinez, E., Lam, C., Crighton, T., Sim, E., Gall, M., Donnan, E. J., Marais, B. J., & Sintchenko, V. (2023a). Exploring programmatic indicators of tuberculosis control that incorporate routine Mycobacterium tuberculosis sequencing in low incidence settings: A comprehensive (2017–2021) patient cohort analysis. The Lancet Regional Health - Western Pacific, 41, 100910. https://doi.org/10.1016/j.lanwpc.2023.100910
Zhang, X., Martinez, E., Lam, C., Crighton, T., Sim, E., Gall, M., Donnan, E. J., Marais, B. J., & Sintchenko, V. (2023b). Exploring programmatic indicators of tuberculosis control that incorporate routine Mycobacterium tuberculosis sequencing in low incidence settings: A comprehensive (2017–2021) patient cohort analysis. The Lancet Regional Health - Western Pacific, 41, 100910. https://doi.org/10.1016/j.lanwpc.2023.100910
التنزيلات
منشور
إصدار
القسم
الرخصة
الحقوق الفكرية (c) 2026 Modern Journal of Health and Applied Sciences

هذا العمل مرخص بموجب Creative Commons Attribution-NonCommercial 4.0 International License.
The users are free to:
- Share — copy and redistribute the material in any medium or format.
- Adapt — remix, transform, and build upon the material.
The licensor cannot revoke these freedoms as long as you follow the license terms.






