DOI QR코드

DOI QR Code

Frequency and Type of Disputed rpoB Mutations in Mycobacterium tuberculosis Isolates from South Korea

  • Jo, Kyung-Wook (Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Soyeon (YD R&D Center, YD Diagnostics) ;
  • Kang, Mi Ran (YD R&D Center, YD Diagnostics) ;
  • Sung, Heungsup (Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Mi-Na (Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Shim, Tae Sun (Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2016.11.28
  • Accepted : 2017.03.30
  • Published : 2017.07.31

Abstract

Background: A disputed rpoB mutation is a specific type of rpoB mutation that can cause low-level resistances to rifampin (RIF). Here, we aimed to assess the frequency and types of disputed rpoB mutations in Mycobacterium tuberculosis isolates from South Korea. Methods: Between August 2009 and December 2015, 130 patients exhibited RIF resistance on the MTBDRplus assay at Asan Medical Center. Among these cases, we identified the strains with disputed rpoB mutation by rpoB sequencing analysis, as well as among the M. tuberculosis strains from the International Tuberculosis Research Center (ITRC). Results: Among our cases, disputed rpoB mutations led to RIF resistance in at least 6.9% (9/130) of the strains that also exhibited RIF resistance on the MTBDRplus assay. Moreover, at the ITRC, sequencing of the rpoB gene of 170 strains with the rpoB mutation indicated that 23 strains (13.5%) had the disputed mutations. By combining the findings from the 32 strains from our center and the ITRC, we identified the type of disputed rpoB mutation as follows: CTG511CCG (L511P, n=8), GAC516TAC (D516Y, n=8), CTG533CCG (L533P, n=8), CAC526CTC (H526L, n=4), CAC526AAC (H526N, n=3), and ATG515GTG (M515V, n=1). Conclusion: Disputed rpoB mutations do not seem to be rare among the strains exhibiting RIF resistance in South Korea.

Keywords

References

  1. Park JS. Issues related to the updated 2014 Korean guidelines for tuberculosis. Tuberc Respir Dis 2016;79:1-4. https://doi.org/10.4046/trd.2016.79.1.1
  2. Zhang Y, Yew WW. Mechanisms of drug resistance in Mycobacterium tuberculosis : update 2015. Int J Tuberc Lung Dis 2015;19:1276-89. https://doi.org/10.5588/ijtld.15.0389
  3. Telenti A, Imboden P, Marchesi F, Lowrie D, Cole S, Colston MJ, et al. Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis . Lancet 1993;341:647-50. https://doi.org/10.1016/0140-6736(93)90417-F
  4. Ocheretina O, Escuyer VE, Mabou MM, Royal-Mardi G, Collins S, Vilbrun SC, et al. Correlation between genotypic and phenotypic testing for resistance to rifampin in Mycobacterium tuberculosis clinical isolates in Haiti: investigation of cases with discrepant susceptibility results. PLoS One 2014;9:e90569. https://doi.org/10.1371/journal.pone.0090569
  5. Ho J, Jelfs P, Sintchencko V. Phenotypically occult multidrugresistant Mycobacterium tuberculosis : dilemmas in diagnosis and treatment. J Antimicrob Chemother 2013;68:2915-20. https://doi.org/10.1093/jac/dkt284
  6. van Ingen J, Aarnoutse R, de Vries G, Boeree MJ, van Soolingen D. Low-level rifampicin-resistant Mycobacterium tuberculosis strains raise a new therapeutic challenge. Int J Tuberc Lung Dis 2011;15:990-2. https://doi.org/10.5588/ijtld.10.0127
  7. Van Deun A, Aung KJ, Hossain A, de Rijk P, Gumusboga M, Rigouts L, et al. Disputed rpoB mutations can frequently cause important rifampicin resistance among new tuberculosis patients. Int J Tuberc Lung Dis 2015;19:185-90. https://doi.org/10.5588/ijtld.14.0651
  8. Huitric E, Werngren J, Jureen P, Hoffner S. Resistance levels and rpoB gene mutations among in vitro-selected rifampinresistant Mycobacterium tuberculosis mutants. Antimicrob Agents Chemother 2006;50:2860-2. https://doi.org/10.1128/AAC.00303-06
  9. Cavusoglu C, Turhan A, Akinci P, Soyler I. Evaluation of the genotype MTBDR assay for rapid detection of rifampin and isoniazid resistance in Mycobacterium tuberculosis isolates. J Clin Microbiol 2006;44:2338-42. https://doi.org/10.1128/JCM.00425-06
  10. Ramaswamy S, Musser JM. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis : 1998 update. Tuber Lung Dis 1998;79:3-29. https://doi.org/10.1054/tuld.1998.0002
  11. Jeon D. Medical management of drug-resistant tuberculosis. Tuberc Respir Dis 2015;78:168-74. https://doi.org/10.4046/trd.2015.78.3.168
  12. Song T, Park Y, Shamputa IC, Seo S, Lee SY, Jeon HS, et al. Fitness costs of rifampicin resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the beta' subunit of RNA polymerase. Mol Microbiol 2014;91:1106-19. https://doi.org/10.1111/mmi.12520
  13. Hain Lifescience. Genotype MTBDRplus ver 2.0 [Internet]. Nehren: Hain Lifescience; 2017 [cited 2017 Jan 2]. Available from: http://www.hain-lifescience.de/en/products/microbiology/mycobacteria/tuberculosis/genotype-mtbdrplus.html.
  14. Definitions and reporting framework for tuberculosis: 2013 revision [Internet]. Geneva: World Health Organization; 2017 [cited 2017 Jan 2]. Available from: http://apps.who.int/iris/bitstream/10665/79199/1/9789241505345_eng.pdf.
  15. Van Deun A, Aung KJ, Bola V, Lebeke R, Hossain MA, de Rijk WB, et al. Rifampin drug resistance tests for tuberculosis: challenging the gold standard. J Clin Microbiol 2013;51:2633-40. https://doi.org/10.1128/JCM.00553-13
  16. Andres S, Hillemann D, Rusch-Gerdes S, Richter E. Occurrence of rpoB mutations in isoniazid-resistant but rifampinsusceptible Mycobacterium tuberculosis isolates from Germany. Antimicrob Agents Chemother 2014;58:590-2. https://doi.org/10.1128/AAC.01752-13
  17. Kambli P, Ajbani K, Sadani M, Nikam C, Shetty A, Udwadia Z, et al. Defining multidrug-resistant tuberculosis: correlating GenoType MTBDRplus assay results with minimum inhibitory concentrations. Diagn Microbiol Infect Dis 2015;82:49-53. https://doi.org/10.1016/j.diagmicrobio.2015.01.009
  18. Williams DL, Spring L, Collins L, Miller LP, Heifets LB, Gangadharam PR, et al. Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis . Antimicrob Agents Chemother 1998;42:1853-7.
  19. Yakrus MA, Driscoll J, Lentz AJ, Sikes D, Hartline D, Metchock B, et al. Concordance between molecular and phenotypic testing of Mycobacterium tuberculosis complex isolates for resistance to rifampin and isoniazid in the United States. J Clin Microbiol 2014;52:1932-7. https://doi.org/10.1128/JCM.00417-14
  20. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update [Internet]. Geneva: World Health Organization; 2016 [cited 2017 Jan 2]. Available from: http://www.who.int/tb/MDRTBguidelines2016.pdf.
  21. van Ingen J, Aarnoutse RE, Donald PR, Diacon AH, Dawson R, Plemper van Balen G, et al. Why do we use 600 mg of rifampicin in tuberculosis treatment? Clin Infect Dis 2011;52:e194-9. https://doi.org/10.1093/cid/cir184
  22. Jindani A, Borgulya G, de Patino IW, Gonzales T, de Fernandes RA, Shrestha B, et al. A randomised Phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis. Int J Tuberc Lung Dis 2016;20:832-8. https://doi.org/10.5588/ijtld.15.0577
  23. Williamson DA, Roberts SA, Bower JE, Vaughan R, Newton S, Lowe O, et al. Clinical failures associated with rpoB mutations in phenotypically occult multidrug-resistant Mycobacterium tuberculosis . Int J Tuberc Lung Dis 2012;16:216-20. https://doi.org/10.5588/ijtld.11.0178
  24. Pang Y, Ruan YZ, Zhao J, Chen C, Xu CH, Su W, et al. Diagnostic dilemma: treatment outcomes of tuberculosis patients with inconsistent rifampicin susceptibility. Int J Tuberc Lung Dis 2014;18:357-62. https://doi.org/10.5588/ijtld.13.0459

Cited by

  1. Mutations of rpoB, katG, inhA and ahp genes in rifampicin and isoniazid-resistant Mycobacterium tuberculosis in Kyrgyz Republic vol.18, pp.None, 2017, https://doi.org/10.1186/s12866-018-1168-x
  2. Discordances between molecular assays for rifampicin resistance in Mycobacterium tuberculosis : frequency, mechanisms and clinical impact vol.75, pp.5, 2017, https://doi.org/10.1093/jac/dkz564
  3. 16S and 23S rRNA Gene Mutation Independent Multidrug Resistance of Non-Tuberculous Mycobacteria Isolated from South Korean Soil vol.8, pp.8, 2020, https://doi.org/10.3390/microorganisms8081114
  4. Diagnostic Evaluation of Non-Interpretable Results Associated with rpoB Gene in Genotype MTBDRplus Ver 2.0 vol.83, pp.4, 2017, https://doi.org/10.4046/trd.2020.0039
  5. Performance Assessment of Xpert MTB/RIF Assay for Detecting Pulmonary Tuberculosis and Rifampin Resistance in a Tertiary Care Hospital in Korea vol.74, pp.6, 2017, https://doi.org/10.7883/yoken.jjid.2020.978
  6. Whole Genome Sequencing of Drug Resistant and Drug Susceptible Mycobacterium tuberculosis Isolates From Tigray Region, Ethiopia vol.12, pp.None, 2017, https://doi.org/10.3389/fmicb.2021.743198
  7. Low-Level Rifampin Resistance and rpoB Mutations in Mycobacterium tuberculosis: an Analysis of Whole-Genome Sequencing and Drug Susceptibility Test Data in New York vol.59, pp.4, 2017, https://doi.org/10.1128/jcm.01885-20
  8. Disputed rpoB Mutations in Mycobacterium tuberculosis and Tuberculosis Treatment Outcomes vol.65, pp.7, 2017, https://doi.org/10.1128/aac.01573-20
  9. Head-to-Head Comparison between Xpert MTB/RIF Assay and Real-Time Polymerase Chain Reaction Assay Using Bronchial Washing Specimens for Tuberculosis Diagnosis vol.85, pp.1, 2017, https://doi.org/10.4046/trd.2021.0100