Skip to main content

Advertisement

Log in

Characterization of mutations in the rpoB gene conferring rifampicin resistance in Mycobacterium tuberculosis complex isolated from lymph nodes of slaughtered cattle from South Africa

  • Environmental Microbiology - Research Paper
  • Published:
Brazilian Journal of Microbiology Aims and scope Submit manuscript

Abstract

Tuberculosis (TB) is an ongoing public health care, with the state of affairs exacerbated by the growth of anti-TB drug-resistant forms in South Africa. Not much attention is given to zoonotic TB. Thus, this study aimed to determine the presence of rpoB mutations among Mycobacterium tuberculosis complex (MTBC) isolates of lymph nodes from slaughtered cattle. A count of 14,950 carcasses from selected abattoirs were examined for nodular lesions and enlarged lymph nodes; 376 lymph nodes were cultured for MTBC. Positive isolates were tested for drug sensitivity against three anti-TB drugs, rifampicin, isoniazid, and ethambutol, using the Lowenstein-Jensen proportion method. Rifampicin-resistant isolates were sequenced, and spoligotyping was performed for lineage classification. A total of 162 isolates were confirmed as MTBC and 42 isolates were resistant to rifampicin. All rifampicin-resistant isolates carried the H526D rpoB mutation, and almost all of them carried an additional nonsynonymous nucleotide substitution in the hot spot region, in three other codons (510, 516 and 522). In total, 5 different mutations at four codons are reported, including one isolate showing 3 of them which has never been reported in South Africa. In addition, we report 4 different spoligo patterns, with 34 isolates known and 8 unknown spoligotype international types. From the known clades, 5 (11.9%) isolates were identified as Bov_4 caprae lineage, 29 (69%) Beijing, and 8 (19.1%) remaining unknown clades. The detection of MTBC-resistant patterns from cattle lymph nodes (Eastern Cape, South Africa) necessitates the investigation of other possible routes of MTBC transmission.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Nguyen L (2016) Antibiotic resistance mechanisms in M. tuberculosis: an update. Arch Toxicol 90(7):1585–1604. https://doi.org/10.1007/s00204-016-1727-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. World Health Organization (2019) Global Tuberculosis Report. Available from https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1. Accessed 15 September 2019

  3. World Health Organization (2014) Xpert MTB/RIF Implementation Manual. Technical and Operational 'How-to Practical Considerations Geneva. Available from https://apps.who.int/iris/bitstream/handie/10665/112469/9789241506700_eng.pdf,jsessionid=749CC4FC08848FBB9534537521F02415?sequence=l. Accessed 23 October 2019

  4. Statistics South Africa (2015) Mortality and causes of death in South Africa: findings from death notification Available from http://www.statssa.gov.za/publications/P03093/P030932015.pdf. Accessed 23 October 2019

  5. World Health Organization (2017) Global Tuberculosis Report Geneva. Available from http://apps.who.int/iris/bitstream/handle/10665/259366/9789241565516-eng:pdf?sequence=l. Accessed 20 October 2019

  6. Zhang M, Yue J, Yang Y, Zhang H, Lei J, Jin R, Zhang XL, Wang HH (2005) Detection of mutations associated with isoniazid resistance in Mycobacterium tuberculosis isolates from China. J Clin Microbiol 43(11):5477–5482

    Article  CAS  Google Scholar 

  7. Somoskovi A, Parsons LM, Salfinger M (2001) The molecular basis of resistance to isoniazid, rifampicin, and pyrazinamide in Mycobacterium tuberculosis. Respir Res 2:164–168

    Article  CAS  Google Scholar 

  8. Ormerod LP, Maynard P, White R, Burch K (2015) Drug resistance trends in Mycobacterium tuberculosis: Blackburn 2000-2009 completion of 50 years continuous surveillance. J Infect Pulm Dis 1(1). https://doi.org/10.16966/2470-3176.103

  9. Telenti A, Imboden P, Marchesi F (1993) Direct, automated detection of rifampicin-resistant Mycobacterium tuberculosis by polymerase chain reaction and single-strand conformation polymorphism analysis. Antimicrob Agents Chemother 37:2054–2058

    Article  CAS  Google Scholar 

  10. National Department of Health, South Africa (2013) Management of drug-resistant tuberculosis. Policy guidelines South Africa. Available from http://www.health-e.org.za/wp-content/uploads/2014/06/MDR-TB-Clinical-Guidelines-Updated-Jan-2013.pdf. Accessed 27 June 2019

  11. Telenti A, Honore N, Bernasconi C, March J, Ortega HT, Cole ST (1997) Genotyping assessment of isoniazid and rifampicin resistance in Mycobacterium tuberculosis: a blind study at reference laboratory level. J Clin Microbiol 35:719–723. https://doi.org/10.1128/JCM.00425-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ismai NM, Mvusi L, Nanoo A (2018) Prevalence of drug-resistant tuberculosis and imputed burden in South Africa: a national and sub-national cross-sectional survey. Lancet Infect Dis 18(8):836. https://doi.org/10.1016/S1473-3099(18)30401-8

    Article  Google Scholar 

  13. World Health Organization (2018) Global Tuberculosis Report 2018. Available from https://reliefweb.int/sites/reliefweb.int/files/resources/9789241565646-eng.pdf. Accessed 23 October 2019

  14. Mahwire ΤC, Zunza M, Marukutira Τ, Naidoo Ρ (2019) Impact of Xpert MTB/RIF assay on multidrug-resistant tuberculosis treatment outcomes in a health district in South Africa. SAMJ 109(4):259–263. https://doi.org/10.7196/SAMJ.2019.v109i4.13180

    Article  CAS  PubMed  Google Scholar 

  15. National Institute for Communicable Diseases (2014) South African Tuberculosis Drug Resistance Survey 2012–2014 South Africa. Available from http://www.nicd.ac.za/assets/files/K-12750NICDNationalSurveyReport_Dev_Vll-LR.pdf. Accessed 23 May 2019

  16. Kapur V, Li LL, Iordanescu S, Hamrick MR, Wanger A (1994) Characterization by automated DNA sequencing of mutations in the gene (rpoB) encoding the RNA polymerase beta subunit in rifampicin-resistant Mycobacterium tuberculosis strains from New York City and Texa. J Clin Microbiol 32:1095–1098

    Article  CAS  Google Scholar 

  17. Ohno H, Koga H, Kohno S (1996) Relationship between rifampicin MICs for and rpoB mutations of Mycobacterium tuberculosis strains isolated in Japan. Antimicrob Agents Chemother 40:1053–1056

    Article  CAS  Google Scholar 

  18. Hirano K, Abe C, Takahashi M (1999) Mutations in the rpoB gene of rifampin-resistant Mycobacterium tuberculosis strains isolated mostly in Asian countries and their rapid detection by line probe assay. J Clin Microbiol 37(8):2663–2666

    Article  CAS  Google Scholar 

  19. World Health Organization (2009) Multidrug and extensively drug-resistant TB (M/XDR-TB): global report of surveillance and response pdf. Geneva

  20. Bhembe NL, Nwodo UU, Govender S, Hayes C, Ndip RN, Okoh AI et al (2014) Molecular detection and characterization of resistant genes in Mycobacterium tuberculosis complex from DNA isolated from tuberculosis patients in the Eastern Cape Province South Africa. BMC Infect Dis 14:479. https://doi.org/10.1186/1471-2334-14-479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Steingart KR, Schiller I, Hörne DJ, Pai M, Boehme CC, Dendukuri N (2014) Xpert* MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev 1:CD009593. https://doi.org/10.1002/14651858.CD009593.pub3

    Article  Google Scholar 

  22. Silaigwana B, Green E, Ndip RN (2012) Molecular detection and drug resistance of Mycobacterium tuberculosis complex from cattle at a dairy farm in the Nkonkobe Region of South Africa: a pilot study. Int J Environ Res Public Health 9:2045–2056. https://doi.org/10.3390/ijerph9062045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bhembe NL, Jaja IF, Nwodo UU, Okoh AI, Green E (2017) Prevalence of tuberculous lymphadenitis in slaughtered cattle in Eastern Cape, South Africa. Int J Iinfect Dis 61:27–37. https://doi.org/10.1016/j.ijid.2017.05.005

    Article  Google Scholar 

  24. Bhembe NL, Nwodo UU, Okoh AI, Obi CL, Mabinya LV, Green E (2019) Clonality and genetic profiles of drug-resistant Mycobacterium tuberculosis in the Eastern Cape Province, South Africa. MicrobiolOpen 8(3):e00449. https://doi.org/10.1002/mbo3.449

    Article  CAS  Google Scholar 

  25. Berg S, Firdessa R, Habtamu M, Gadisa E, Mengistu A (2009) The burden of mycobacterial disease in Ethiopian cattle: implications for public health. PLoS One 4:e5068

    Article  Google Scholar 

  26. Yates M, Drobniewski F, Wilson S (2002) Evaluation of a rapid PCR-based epidemiological typing for routine studies of Mycobacterium tuberculosis. J Clin Microbiol 40:712–714. https://doi.org/10.1128/JCM.40.2.712-714.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Madhavan HN, Therese KL, Gunisha P, Jayanthi U, Biswas J (2000) Polymerase chain reaction for detection of Mycobacterium tuberculosis in epiretinal membrane in Eales’ disease. Invest Ophthalmol Vis Sci 41:822–825

    CAS  PubMed  Google Scholar 

  28. World Health Organization (2009) Guidelines for surveillance of drug resistance in tuberculosis, 4th ed. Document WHO/HTM/TB/2009, 422. World Health Organization, Geneva

    Google Scholar 

  29. Stroup S, Pholwat S, Heysell SK, Khan E, Ferdous SS, Ahmed S (2014) Discordance across several methods for drug susceptibility testing of drug-resistant Mycobacterium tuberculosis isolates in a single laboratory. J Clin Microbiol 52(1):156–163. https://doi.org/10.1128/JCM.02378-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ali A, Hasan Z, McNerney R, Mallard K, Hill-Cawthorne G, Coll F et al (2015) Whole-genome sequencing based characterization of extensively drug-resistant Mycobacterium tuberculosis isolates from Pakistan. PLoS One 10(2):e0117771. https://doi.org/10.1371/journal.pone.0117771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ovchinnikov YA, Monastyrskaya GS, Gubanov VV, Guryev SO, Chertov OY, Modyanov NN et al (1981) The primary structure of Escherichia coli RNA polymerase nucleotide sequence of the rpoB gene and amino-acid sequence of the beta subunit. Eur J Biochem 116:621–629. https://doi.org/10.1111/j.1432-1033.1981.tb05381.x

    Article  CAS  PubMed  Google Scholar 

  32. Caimi K, Romano MI, Aliso A, Zumarraga M, Bigi F, Cataldi A (2001) Sequence analysis of the direct repeat region in Mycobacterium bovis. J Clin Microbiol 39:1067–1072. https://doi.org/10.1128/JCM.39.3.1067-1072.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yingyu C, Yanjie C, Quantao D, Tao L, Jie X, Jun C et al (2009) Potential challenges to the Stop TB Plan for humans in China; cattle maintain M. bovis and M. tuberculosis. Tuberculosis 89:95–100. https://doi.org/10.1016/j.tube.2008.07.003

    Article  CAS  Google Scholar 

  34. Foddai A, Nielsen LR, Krogh K, Albania L (2015) Assessment of the probability of introduction of bovine tuberculosis to Danish cattle farms via imports of live cattle from abroad and immigrant workers. Prev Vet Med 22(3):306–317. https://doi.org/10.1016/j.prevetmed.2015.08.007

    Article  Google Scholar 

  35. Miller LP, Crawford JT, Shinnick TM (1994) The rpoB gene of Mycobacterium tuberculosis. Antimicrob Agents Chemother 38(4):805–811

    Article  CAS  Google Scholar 

  36. Chaves F, Alonso-Sanz M, Rebollo MJ, Tercero JC, Jimenez MS (2000) rpoB mutations as an epidemiologic marker in rifampin-resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis 4:765–770. https://doi.org/10.1128/JCM.39.5.1813-1818.2001

    Article  CAS  PubMed  Google Scholar 

  37. Klein JL, Brown TJ, French GL (2001) Rifampin resistance in Mycobacterium kansasii is associated with rpoB mutations. Antimicrob Agents Chemother 45:3056–3058. https://doi.org/10.1128/AAC.45.11.3056-3058.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mitchison DA, Nunn AJ (1986) Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis 133:423–430. https://doi.org/10.1164/arrd.1986.133.3.423

    Article  CAS  PubMed  Google Scholar 

  39. Cavusoglu C, Hilmioglu S, Guneri S, Bilgic A (2002) Characterization of rpoB mutations in rifampin-resistant clinical isolates of Mycobacterium tuberculosis from Turkey by DNA sequencing and line probe assay. J Clin Microbiol 40(12):4435–4438. https://doi.org/10.1128/jcm.40.12.4435-4438.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Torres MJ, Criado A, Aznar J (2003) Improved real-time PCR for rapid detection of rifampicin and isoniazid resistance of Mycobacterium tuberculosis in clinical isolates. Diagn Microbiol Infect Dis 45(3):207–212. https://doi.org/10.1016/s0732-8893(02)00521-7

    Article  CAS  PubMed  Google Scholar 

  41. Matsiota-Bernard P, Vrioni G, Marinis E (1998) Characterization of rpoB mutations in rifampin-resistant clinical Mycobacterium tuberculosis isolates from Greece. J Clin Microbiol 36:20–23

    Article  CAS  Google Scholar 

  42. Pozzi G, Meloni M, Iona E, Orro G, Thorensen OF, Ricci ML et al (1999) rpoB mutations in multidrug-resistant strains of Mycobacterium tuberculosis isolated in Italy. J Clin Microbiol 37:1197–1199

    Article  CAS  Google Scholar 

  43. Schilke K, Weyer K, Bretzel G, Amthor B, Brandt J, Sticht-Groh V, Fourie PB, Haas WH (1999) Universal pattern of rpoB gene mutations among multidrug-resistant isolates of Mycobacterium tuberculosis complex from Africa. Int J Tuberc Lung Dis 3(7):620–626

    CAS  PubMed  Google Scholar 

  44. Valim ARM, Rosetti MLR, Ribeiro MO, Zaha A (2000) Mutations in the rpoB gene of multidrug-resistant Mycobacterium tuberculosis isolates from Brazil. J Clin Microbiol 38:3119–3122

    Article  CAS  Google Scholar 

  45. Mani C, Selvakumar N, Kumar V, Narayanan S, Narayanan PR (2003) Comparison of DNA sequencing, PCR-SSCP and PhaB assays with indirect sensitivity testing for detection of rifampicin resistance in Mycobacterium tuberculosis. Int J Tuberc Lung Dis 7:652–659

    CAS  PubMed  Google Scholar 

  46. Green E, Obi LC, Nchabeleng M, de Villiers BE, Sein PP, Letsoalo T, Hoosen AA, Bessong PO (2015) Molecular characterization of resistant Mycobacterium tuberculosis isolates from Dr. George Mukhari Hospital, Pretoria, South Africa. SAJEI 23(3):11–14. https://doi.org/10.1080/10158782.2008.11441316

    Article  Google Scholar 

  47. Evans J, Stead MC, Nicol MP, Segal H (2009) Rapid genotypic assays to identify drug-resistant Mycobacterium tuberculosis in South Africa. J Antimicrob Chemother 63:11–16. https://doi.org/10.1093/jac/dkn433

    Article  CAS  PubMed  Google Scholar 

  48. Green E, Obi LC, Okoh AI, Nchabeleng M, de Villiers BE, Letsoalo T et al (2013) IS6110 restriction fragment length polymorphism typing of drug-resistant Mycobacterium tuberculosis strains from Northeast South Africa. J Health Popul Nutr 31(1):1–10

    Article  Google Scholar 

  49. Williamson DA, Roberts SA, Bower JE, Freeman JT, Henderson G, Roberts SA (2012) Clinical failures associated with rpoB mutations in phenotypically occult multidrug-resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis 16:216–220. https://doi.org/10.5588/ijtld.11.0178

    Article  CAS  PubMed  Google Scholar 

  50. Zenteno-Cuevas R, Zenteno JC, Cuellar A, Cuevas B, Sampieri CL, Riviera JE et al (2009) Mutations in rpoB and katG genes in Mycobacterium isolates from the Southeast of Mexico. Mem Inst Oswaldo Cruz Rio de Janeiro 104(3):468–472. https://doi.org/10.1590/s0074-02762009000300012

    Article  CAS  Google Scholar 

  51. Tan Y, Hu Z, Zhao Y, Cai X, Luo C, Zou C et al (2011) The beginning of the rpoB gene in addition to the rifampicin resistance determination region might be needed for identifying rifampin/rifabutin cross-resistance in multidrug-resistant Mycobacterium tuberculosis isolates from Southern China. J Clin Microbiol 5:81–85. https://doi.org/10.1128/JCM.05092-11

    Article  CAS  Google Scholar 

  52. Williams DL, Waguespack C, Eisenach K, Crawford JT, Porteals F, Salfinger M et al (1994) Characterization of rifampin resistance in pathogenic mycobacteria. Antimicrob Agents Chemother 38:2380–2386

    Article  CAS  Google Scholar 

  53. Yue J, Shi W, Xie J, Li Y, Zeng E, Wang H (2003) Mutations in the rpoB gene of multidrug-resistant Mycobacterium tuberculosis isolates from China. J Clin Microbiol 41(5):2209–2212. https://doi.org/10.1128/jcm.41.5.2209-2212.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Prammananan T, Cheunoy W, Taechamahapun D, Yorsangsukkamol J, Phunpruch S, Phdarat P et al (2008) Distribution of rpoB mutations among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains from Thailand and development of a rapid method for mutation detection. J Clin Microbiol Infect 14:446–453. https://doi.org/10.1111/j.1469-0691.2008.01951.x

    Article  CAS  Google Scholar 

  55. Huitric E, Werngren J, Jure’en P, Hoffner S (2006) Resistance levels and rpoB gene mutations among in vitro-selected rifampin-resistant Mycobacterium tuberculosis mutants. J Antimicrob Agents Chemother 50(8):2860–2862. https://doi.org/10.1128/AAC.00303-06

    Article  CAS  Google Scholar 

  56. Chen L, Gan X, Li N, Wang J, Li K, Zhang H (2010) rpoB gene mutation profile in rifampicin-resistant Mycobacterium tuberculosis clinical isolates from Guizhou, one of the highest incidence rate regions in China. J Antimicrob Chemother 65(6):1299–1301. https://doi.org/10.1093/jac/dkq102

    Article  CAS  PubMed  Google Scholar 

  57. Izadi N, Derakhshan M, Taleghanki HB, Jamehdar SA, Eidgahi MRA, Ghazvini K (2015) Molecular characteristics of rifampin resistance among Mycobacterium tuberculosis strains isolated in northeast of Iran. IJPBS 4:95–102. https://doi.org/10.4314/ejhs.v28i3.7

    Article  CAS  Google Scholar 

  58. Ramaswamy S, Musser JM (1998) Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Int J Tuberc Lung Dis 79:3–29. https://doi.org/10.1054/tuld.1998.0002

    Article  CAS  Google Scholar 

  59. Bobadilla-del-Valle M, Ponce-de-Leon A, Arenas-Huertero C, Vargas-Alarcon G, Kato-Maeda M, Small PM et al (2001) rpoB gene mutations in rifampin-resistant Mycobacterium tuberculosis identified by polymerase chain reaction single-stranded conformational polymorphism. Emerg Infect Dis 7:1010–1013. https://doi.org/10.3201/eid0706.010615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Heep M, Brandstatter B, Rieger U, Lehn N, Richter E, Rusch-Gerdes S, Niemann S (2001) Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates. J Clin Microbiol 39:107–110. https://doi.org/10.1128/JCM.39.1.107-110.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sougakoff W, Rodrigue M, Truffot-Pernot C, Renard M, Durin N, Szpytma M (2004) Use of a high-density DNA probe array for detecting mutations involved in rifampicin resistance in Mycobacterium tuberculosis. Clin Microbiol Infect 10:289–294. https://doi.org/10.1111/j.1198-743X.2004.00889.x

    Article  CAS  PubMed  Google Scholar 

  62. Ahmad S, Mokaddas E (2005) The occurrence of rare rpoB mutations in rifampicin-resistant clinical Mycobacterium tuberculosis isolates from Kuwait. Int J Antimicrob Agents 26:205–212. https://doi.org/10.1016/j.ijantimicag.2005.06.009

    Article  CAS  PubMed  Google Scholar 

  63. Nakata N, Kai M, Makino M (2012) Mutation analysis of mycobacterial rpoB genes and rifampicin resistance using recombinant Mycobacterium smegmatis. Antimicrob Agents Chemother 56(4):2008–2013. https://doi.org/10.1128/AAC.05831-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Mokrousov I (2004) Multiple rpoB mutants of Mycobacterium tuberculosis and second-order selection. Emerg Infect Dis 10(7):1337–1338. https://doi.org/10.3201/eid1007.030598

    Article  PubMed  PubMed Central  Google Scholar 

  65. Klopper M, Warren RM, Hayes C, van Pittius NCJ, Streicher EM, Müller B (2013) Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa. Emerg Infect Dis 19(3):449–455. https://doi.org/10.3201/EID1903.120246

    Article  PubMed  PubMed Central  Google Scholar 

  66. Rad ME, Bifani P, Martin C, Kremer K, Samper S, Rauzier J (2003) Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerg Infect Dis 9:838–845. https://doi.org/10.3201/eid0907.020803

    Article  CAS  PubMed Central  Google Scholar 

  67. Bhembe NL, Green E (2020) Molecular epidemiological study of multidrug-resistant tuberculosis isolated from sputum samples in Eastern Cape, South Africa. Infect Genet Evol 80:104182. https://doi.org/10.1016/j.meegid.2020.104182

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to extend their appreciation to the University of Fort Hare and the University of Johannesburg for allowing us to conduct this study.

Funding

The National Research Foundation (NRF) of South Africa funded this work; we are grateful to them.

Author information

Authors and Affiliations

Authors

Contributions

NLB collected samples, executed the research, and prepared the manuscript. EG was involved in the study design and supervision, helped with findings and interpretation, contributed to the manuscript and proofread the final version of the manuscript.

Corresponding author

Correspondence to Nolwazi L. Bhembe.

Ethics declarations

Conflict of interests

The authors declare that they have no conflict of interest.

Ethics approval

This project was approved by the University of Fort Hare Research Ethics Committee (UREC), and an ethical clearance certificate, REC-270710-028-RA, was issued.

Additional information

Responsible Editor: Sylvia Cardoso Leão

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhembe, N.L., Green, E. Characterization of mutations in the rpoB gene conferring rifampicin resistance in Mycobacterium tuberculosis complex isolated from lymph nodes of slaughtered cattle from South Africa. Braz J Microbiol 51, 1919–1927 (2020). https://doi.org/10.1007/s42770-020-00356-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42770-020-00356-4

Keywords

Navigation