Volume 11, Issue 4 (12-2023)                   JoMMID 2023, 11(4): 179-184 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Madadi-Goli N, Ahmadi K, Khanipour S, Pourazar Dizaji S, Nasehi M, Siadat S D, et al . Investigating the Mutations in atpE and Rv0678 Genes in Mycobacterium Tuberculosis Clinical Isolates. JoMMID 2023; 11 (4) :179-184
URL: http://jommid.pasteur.ac.ir/article-1-615-en.html
Investigating the Mutations in atpE and Rv0678 Genes in Mycobacterium Tuberculosis Clinical Isolates
Nahid Madadi-Goli , Kamal Ahmadi , Sharareh Khanipour , Shahin Pourazar Dizaji , Mahshid Nasehi , Seyed Davar Siadat , Farzam Vaziri , Abolfazl Fateh
1Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; 2Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
Abstract:   (703 Views)
Introduction: Tuberculosis (TB) caused by the bacterium Mycobacterium tuberculosis remains a critical global public health concern due to the high morbidity and mortality rates. Mutation in atpE and Rv0678 genes contributes to drug resistance in M. tuberculosis. This study investigates the antibiotic resistance patterns and mutations in atpE and Rv0678 genes in 22 M. tuberculosis clinical isolates. Methods: Drug susceptibility testing (DST) for rifampin, isoniazid, streptomycin, capreomycin, ofloxacin, kanamycin, and ethambutol was conducted using the proportional method. This was followed by determining the minimum inhibitory concentration (MIC) for bedaquiline (BDQ) via the microplate Alamar blue assay (MABA). Genomic regions encompassing atpE and Rv0678 genes were amplified and sequenced for mutation analysis. Data analysis was performed using SPSS software to interpret mutation patterns concerning drug susceptibility profiles. Results: Of 22 isolates, 5 (27.8%) were extensively drug-resistant tuberculosis (XDR-TB), and 13 (72.2%) were multi-drug resistant tuberculosis (MDR-TB). Resistance rates to kanamycin, ofloxacin, capreomycin, and streptomycin were 40.6%, 46.3%, 85%, and 74.6%, respectively. Additionally, phenotypic resistance to bedaquiline was observed in 12 (54.5%) isolates. Sequencing revealed no resistance-conferring mutations in the atpE or Rv0678 genes among the isolates. Conclusion: Our findings showed substantial resistance to first- and second-line drugs in M. tuberculosis clinical isolates. This highlights the necessity for ongoing, comprehensive studies to elucidate the evolving drug resistance patterns and understand the underlying mechanisms in clinical isolates.
Keywords: Mycobacterium tuberculosis, DST, atpE, Rv0678, Bedaquiline, Extensively drug-resistant tuberculosis (XDR-TB), Multi-drug resistant tuberculosis (MDR-TB)
Full-Text [PDF 730 kb]   (179 Downloads)    
Type of Study: Original article | Subject: Anti-microbial agents, resistance and treatment protocols
Received: 2023/11/1 | Accepted: 2023/12/10 | Published: 2024/02/24
References
1. Kamakoli MK, Farmanfarmaei G, Masoumi M, Khanipour S, Gharibzadeh S, Sola C, et al. Prediction of the hidden genotype of mixed infection strains in Iranian tuberculosis patients. Int J Infect Dis. 2020; 95: 22-7. [DOI:10.1016/j.ijid.2020.03.056] [PMID]
2. Mbugi EV, Katale BZ, Siame KK, Keyyu JD, Kendall SL, Dockrell HM, et al. Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania. Tuberculosis. 2015; 95 (2): 170-8. [DOI:10.1016/j.tube.2014.11.006] [PMID] []
3. Bagcchi S. WHO's global tuberculosis report 2022. Lancet Microbe. 2023; 4 (1): e20. [DOI:10.1016/S2666-5247(22)00359-7] [PMID]
4. Raviglione M. XDR-TB: entering the post-antibiotic era? Int J Tuberc Lung Dis. 2006; 10 (11): 1185-7.
5. Horsburgh Jr CR, Barry III CE, Lange C. Treatment of tuberculosis. N Engl J Med. 2015; 373 (22): 2149-60. [DOI:10.1056/NEJMra1413919] [PMID]
6. Rivière E, Verboven L, Dippenaar A, Goossens S, De Vos E, Streicher E, et al. Variants in bedaquiline-candidate-resistance genes: prevalence in bedaquiline-naive patients, effect on MIC, and association with Mycobacterium tuberculosis Lineage. Antimicrob Agents Chemother. 2022; 66 (7): e00322-22. [DOI:10.1128/aac.00322-22] [PMID] []
7. Preiss L, Langer JD, Yildiz Ö, Eckhardt-Strelau L, Guillemont JE, Koul A, et al. Structure of the mycobacterial ATP synthase Fo rotor ring in complex with the anti-TB drug bedaquiline. Sci Adv. 2015; 1 (4): e1500106. [DOI:10.1126/sciadv.1500106] [PMID] []
8. Raju RM, Raju SM, Zhao Y, Rubin EJ. Leveraging Advances in Tuberculosis Diagnosis and Treatment to Address Nontuberculous Mycobacterial Disease. Emerg Infect Dis. 2016; 22 (3): 365-9. [DOI:10.3201/eid2203.151643] [PMID] []
9. Cholo MC, Mothiba MT, Fourie B, Anderson R. Mechanisms of action and therapeutic efficacies of the lipophilic antimycobacterial agents clofazimine and bedaquiline. J Antimicrob Chemother. 2017; 72 (2): 338-53. [DOI:10.1093/jac/dkw426] [PMID]
10. Andries K, Villellas C, Coeck N, Thys K, Gevers T, Vranckx L, et al. Acquired resistance of Mycobacterium tuberculosis to bedaquiline. PloS One. 2014; 9 (7): e102135. [DOI:10.1371/journal.pone.0102135] [PMID] []
11. Ghajavand H, Kargarpour Kamakoli M, Khanipour S, Pourazar Dizaji S, Masoumi M, Rahimi Jamnani F, et al. Scrutinizing the drug resistance mechanism of multi-and extensively-drug resistant Mycobacterium tuberculosis: mutations versus efflux pumps. Antimicrob Resist Infect Control. 2019; 8: 70. [DOI:10.1186/s13756-019-0516-4] [PMID] []
12. Supply P, Lesjean S, Savine E, Kremer K, van Soolingen D, Locht C. Automated high-throughput genotyping for study of global epidemiology of Mycobacterium tuberculosis based on mycobacterial interspersed repetitive units. J Clin Microbiol. 2001; 39 (10): 3563-71. [DOI:10.1128/JCM.39.10.3563-3571.2001] [PMID] []
13. Khoshnood S, Goudarzi M, Taki E, Darbandi A, Kouhsari E, Heidary M, et al. Bedaquiline: Current status and future perspectives. J Glob Antimicrob Resist. 2021; 25: 48-59. [DOI:10.1016/j.jgar.2021.02.017] [PMID]
14. Laws M, Jin P, Rahman KM. Efflux pumps in Mycobacterium tuberculosis and their inhibition to tackle antimicrobial resistance. Trends Microbiol. 2022; 30 (1): 57-68. [DOI:10.1016/j.tim.2021.05.001] [PMID]
15. Bloemberg GV, Keller PM, Stucki D, Trauner A, Borrell S, Latshang T, et al. Acquired Resistance to Bedaquiline and Delamanid in Therapy for Tuberculosis. N Engl J Med. 2015; 373 (20): 1986-8. [DOI:10.1056/NEJMc1505196] [PMID] []
16. Narang A, Giri A, Gupta S, Garima K, Bose M, Varma-Basil M. Contribution of putative efflux pump genes to isoniazid resistance in clinical isolates of Mycobacterium tuberculosis. Int J Mycobacteriol. 2017; 6 (2): 177-83. [DOI:10.4103/ijmy.ijmy_26_17] [PMID]
17. Zhang C, Ouyang Q, Zhou X, Huang Y, Zeng Y, Deng L, et al. In vitro activity of tetracycline analogs against multidrug-resistant and extensive drug resistance clinical isolates of Mycobacterium tuberculosis. Tuberculosis. 2023; 140: 102336. [DOI:10.1016/j.tube.2023.102336] [PMID]
18. Wu SH, Chan HH, Hsiao HC, Jou R. Primary Bedaquiline Resistance Among Cases of Drug-Resistant Tuberculosis in Taiwan. Front Microbiol. 2021; 12: 754249. [DOI:10.3389/fmicb.2021.754249] [PMID] []
19. Hofmann-Thiel S, van Ingen J, Feldmann K, Turaev L, Uzakova GT, Murmusaeva G, et al. Mechanisms of heteroresistance to isoniazid and rifampin of Mycobacterium tuberculosis in Tashkent, Uzbekistan. Eur Respir J. 2009; 33 (2): 368-74. [DOI:10.1183/09031936.00089808] [PMID]
20. Siddiqi S, Ahmed A, Asif S, Behera D, Javaid M, Jani J, et al. Direct drug susceptibility testing of Mycobacterium tuberculosis for rapid detection of multidrug resistance using the Bactec MGIT 960 system: a multicenter study. J Clin Microbiol. 2012; 50 (2): 435-40. [DOI:10.1128/JCM.05188-11] [PMID] []
21. Vīksna A, Sadovska D, Berge I, Bogdanova I, Vaivode A, Freimane L, et al. Genotypic and phenotypic comparison of drug resistance profiles of clinical multidrug-resistant Mycobacterium tuberculosis isolates using whole genome sequencing in Latvia. BMC Infect Dis. 2023; 23 (1): 638. [DOI:10.1186/s12879-023-08629-7] [PMID] []
22. Mansoor H, Hirani N, Chavan V, Das M, Sharma J, Bharati M, et al. Clinical utility of target-based next-generation sequencing for drug-resistant TB. Int J Tuberc Lung Dis. 2023; 27 (1): 41-8. [DOI:10.5588/ijtld.22.0138] [PMID] []
23. Morey-León G, Andrade-Molina D, Fernández-Cadena JC, Berná L. Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador. BMC Genom. 2022; 23 (1): 844. [DOI:10.1186/s12864-022-09042-1] [PMID] []
24. Utpat KV, Rajpurohit R, Desai U. Prevalence of pre-extensively drug-resistant tuberculosis (Pre XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) among extra pulmonary (EP) multidrug resistant tuberculosis (MDR-TB) at a tertiary care center in Mumbai in pre Bedaquiline (BDQ) era. Lung India. 2023; 40 (1): 19-23. [DOI:10.4103/lungindia.lungindia_182_22] [PMID] []
25. Nguyen TVA, Anthony RM, Bañuls AL, Nguyen TVA, Vu DH, Alffenaar JC. Bedaquiline Resistance: Its Emergence, Mechanism, and Prevention. Clin Infect Dis. 2018; 66 (10): 1625-30. [DOI:10.1093/cid/cix992] [PMID]
26. Ghajavand H, Kargarpour Kamakoli M, Khanipour S, Pourazar Dizaji S, Masoumi M, Rahimi Jamnani F, et al. High Prevalence of Bedaquiline Resistance in Treatment-Naive Tuberculosis Patients and Verapamil Effectiveness. Antimicrob Agents Chemother. 2019; 63 (3): e02530-18. [DOI:10.1128/AAC.02530-18] [PMID] []
27. Derendinger B, Dippenaar A, de Vos M, Huo S, Alberts R, Tadokera R, et al. High frequency of bedaquiline resistance in programmatically treated drug-resistant TB patients with sustained culture-positivity in Cape Town, South Africa. medRxiv. 2022: 2022.11. 14.22282167. [DOI:10.1101/2022.11.14.22282167]
28. Yang J, Pang Y, Zhang T, Xian X, Li Y, Wang R, et al. Molecular characteristics and in vitro susceptibility to bedaquiline of Mycobacterium tuberculosis isolates circulating in Shaanxi, China. Int J Infect Dis. 2020; 99: 163-70. [DOI:10.1016/j.ijid.2020.07.044] [PMID]
29. Wang M-G, Wu S-Q, He J-Q. Efficacy of bedaquiline in the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis. BMC Infect Dis. 2021; 21 (1): 970. [DOI:10.1186/s12879-021-06666-8] [PMID] []
30. Tong E, Zhou Y, Liu Z, Zhu Y, Zhang M, Wu K, et al. Bedaquiline Resistance and Molecular Characterization of Rifampicin-Resistant Mycobacterium Tuberculosis Isolates in Zhejiang, China. Infect Drug Resist. 2023; 16: 6951-63. [DOI:10.2147/IDR.S429003] [PMID] []
31. Yang JS, Kim KJ, Choi H, Lee SH. Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration Distributions and Resistance-related Gene Mutations in Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Korea. Ann Lab Med. 2018; 38 (6): 563-8. [DOI:10.3343/alm.2018.38.6.563] [PMID] []
32. Guo Q, Bi J, Lin Q, Ye T, Wang Z, Wang Z, Liu L, Zhang G. Whole Genome Sequencing Identifies Novel Mutations Associated With Bedaquiline Resistance in Mycobacterium tuberculosis. Front Cell Infect Microbiol. 2022; 12: 807095. [DOI:10.3389/fcimb.2022.807095] [PMID] []
33. Rahul P, Zeeshan F, Saif H. Efflux pumps in drug resistance of Mycobacterium tuberculosis: a panoramic view. Int J Curr Microbiol Appl Sci. 2014; 3 (8): 528-46.
Add your comments about this article : Your username or Email:
CAPTCHA
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.