Skip to main content

Advertisement

SpringerLink
Log in

Correlation between variable-number tandem-repeat-based genotypes and drug susceptibility in Mycobacterium avium isolates

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Little is known about the correlation between genotype and drug susceptibility in Mycobacterium avium (Mav) strains isolated from patients with Mav infections. To examine whether drug susceptibility profile of Mav is associated with genotype, we carried out variable-number tandem-repeat (VNTR) typing and drug susceptibility testing for Mav isolates from Japanese with nodular-bronchiectasis (NB)-type and cavitary disease (CA)-type diseases. We performed M. avium tandem repeat (MATR)-VNTR typing and drug susceptibility testing by the broth dilution method, using macrolides, rifamycins, ethambutol, isoniazid, aminoglycosides, and quinolones, for Mav isolates from patients with NB and CA-type diseases (NB-Mav and CA-Mav). Based on the VNTR genotyping, the Mav strains were grouped into three clusters. There was no difference with respect to the distribution of NB-Mav and CA-Mav among the clusters. We observed a strong association between VNTR genotype and susceptibility to quinolones (levofloxacin, moxifloxacin, gatifloxacin, sitafloxacin, and garenoxacin) and ethambutol. There was essentially no significant difference in drug susceptibility between NB- and CA-Mav strains, although NB-Mav was somewhat more resistant to fluoroquinolones, especially gatifloxacin, than CA-Mav. There was a significant association between VNTR genotype and susceptibility to quinolones and ethambutol in Mav isolates from Japanese patients.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kasperbauer SH, Daley CL (2008) Diagnosis and treatment of infections due to Mycobacterium avium complex. Semin Respir Crit Care Med 29:569–576

    Article  PubMed  Google Scholar 

  2. Inglis N, McFadden J (1999) Strain typing of the Mycobacterium avium complex. J Infect 38:151–156

    Article  PubMed  CAS  Google Scholar 

  3. Radomski N, Thibault VC, Karoui C et al (2010) Determination of genotypic diversity of Mycobacterium avium subspecies from human and animal origins by mycobacterial interspersed repetitive-unit variable-number tandem-repeat and IS1311 restriction fragment length polymorphism typing methods. J Clin Microbiol 48:1026–1034

    Article  PubMed  CAS  Google Scholar 

  4. Inagaki T, Nishimori K, Yagi T et al (2009) Comparison of a variable-number tandem-repeat (VNTR) method for typing Mycobacterium avium with mycobacterial interspersed repetitive-unit-VNTR and IS1245 restriction fragment length polymorphism typing. J Clin Microbiol 47:2156–2164

    Article  PubMed  CAS  Google Scholar 

  5. Tirkkonen T, Pakarinen J, Rintala E et al (2010) Comparison of variable-number tandem-repeat markers typing and IS1245 restriction fragment length polymorphism fingerprinting of Mycobacterium avium subsp. hominissuis from human and porcine origins. Acta Vet Scand 52:21

    Article  PubMed  Google Scholar 

  6. Thibault VC, Grayon M, Boschiroli ML et al (2007) New variable-number tandem-repeat markers for typing Mycobacterium avium subsp. paratuberculosis and M. avium strains: comparison with IS900 and IS1245 restriction fragment length polymorphism typing. J Clin Microbiol 45:2404–2410

    Article  PubMed  CAS  Google Scholar 

  7. Iseman MD (1989) Mycobacterium avium complex and the normal host: the other side of the coin. N Engl J Med 321:896–898

    Article  PubMed  CAS  Google Scholar 

  8. Reich JM, Johnson RE (1992) Mycobacterium avium complex pulmonary disease presenting as an isolated lingular or middle lobe pattern. The Lady Windermere syndrome. Chest 101:1605–1609

    Article  PubMed  CAS  Google Scholar 

  9. Glassroth J (2008) Pulmonary disease due to nontuberculous mycobacteria. Chest 133:243–251

    Article  PubMed  Google Scholar 

  10. Harada S, Harada Y, Ochiai S et al (2003) A clinical study on cases with pulmonary M. avium complex (MAC) disease followed up for more than 10 years. Kekkaku 78:517–523

    PubMed  Google Scholar 

  11. Falkinham JO 3rd, Iseman MD, de Haas P et al (2008) Mycobacterium avium in a shower linked to pulmonary disease. J Water Health 6:209–213

    PubMed  Google Scholar 

  12. Tatano Y, Yasumoto K, Tomioka H et al (2010) Comparative study for the virulence of Mycobacterium avium isolates from patients with nodular-bronchiectasis- and cavitary-type diseases. Eur J Clin Microbiol Infect Dis 29:801–806

    Article  PubMed  CAS  Google Scholar 

  13. Fitch WM, Margoliash E (1967) Construction of phylogenetic trees. Science 155:279–284

    Article  PubMed  CAS  Google Scholar 

  14. Kikuchi T, Watanabe A, Gomi K et al (2009) Association between mycobacterial genotypes and disease progression in Mycobacterium avium pulmonary infection. Thorax 64:901–907

    Article  PubMed  CAS  Google Scholar 

  15. Yajko DM, Madej JJ, Lancaster MV et al (1995) Colorimetric method for determining MICs of antimicrobial agents for Mycobacterium tuberculosis. J Clin Microbiol 33:2324–2327

    PubMed  CAS  Google Scholar 

  16. Castellanos E, Romero B, Rodríguez S et al (2010) Molecular characterization of Mycobacterium avium subspecies paratuberculosis types II and III isolates by a combination of MIRU-VNTR loci. Vet Microbiol 144:118–126

    Article  PubMed  CAS  Google Scholar 

  17. Killgore G, Thompson A, Johnson S et al (2008) Comparison of seven techniques for typing international epidemic strains of Clostridium difficile: restriction endonuclease analysis, pulsed-field gel electrophoresis, PCR-ribotyping, multilocus sequence typing, multilocus variable-number tandem-repeat analysis, amplified fragment length polymorphism, and surface layer protein A gene sequence typing. J Clin Microbiol 46:431–437

    Article  PubMed  CAS  Google Scholar 

  18. Bull TJ, Sidi-Boumedine K, McMinn EJ et al (2003) Mycobacterial interspersed repetitive units (MIRU) differentiate Mycobacterium avium subspecies paratuberculosis from other species of the Mycobacterium avium complex. Mol Cell Probes 17:157–164

    Article  PubMed  CAS  Google Scholar 

  19. Romano MI, Amadio A, Bigi F et al (2005) Further analysis of VNTR and MIRU in the genome of Mycobacterium avium complex, and application to molecular epidemiology of isolates from South America. Vet Microbiol 110:221–237

    Article  PubMed  CAS  Google Scholar 

  20. Frothingham R, Meeker-O’Connell WA (1998) Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats. Microbiology 144:1189–1196

    Article  PubMed  CAS  Google Scholar 

  21. Skuce RA, McCorry TP, McCarroll JF et al (2002) Discrimination of Mycobacterium tuberculosis complex bacteria using novel VNTR-PCR targets. Microbiology 148:519–528

    PubMed  CAS  Google Scholar 

  22. Roring S, Scott A, Brittain D et al (2002) Development of variable-number tandem repeat typing of Mycobacterium bovis: comparison of results with those obtained by using existing exact tandem repeats and spoligotyping. J Clin Microbiol 40:2126–2133

    Article  PubMed  CAS  Google Scholar 

  23. Dvorska L, Bartos M, Ostadal O et al (2002) IS1311 and IS1245 restriction fragment length polymorphism analyses, serotypes, and drug susceptibilities of Mycobacterium avium complex isolates obtained from a human immunodeficiency virus-negative patient. J Clin Microbiol 40:3712–3719

    Article  PubMed  CAS  Google Scholar 

  24. Ohkusu K, Bermudez LE, Nash KA et al (2004) Differential virulence of Mycobacterium avium strains isolated from HIV-infected patients with disseminated M. avium complex disease. J Infect Dis 190:1347–1354

    Article  PubMed  Google Scholar 

  25. Wu TS, Leu HS, Chiu CH et al (2009) Clinical manifestations, antibiotic susceptibility and molecular analysis of Mycobacterium kansasii isolates from a university hospital in Taiwan. J Antimicrob Chemother 64:511–514

    Article  PubMed  CAS  Google Scholar 

  26. Anh DD, Borgdorff MW, Van LN et al (2000) Mycobacterium tuberculosis Beijing genotype emerging in Vietnam. Emerg Infect Dis 6:302–305

    Article  PubMed  CAS  Google Scholar 

  27. Bifani PJ, Plikaytis BB, Kapur V et al (1996) Mycobacterium tuberculosis clone family. JAMA 275:452–457

    Article  PubMed  CAS  Google Scholar 

  28. Portaels F, Rigouts L, Bastian I (1999) Addressing multidrug-resistant tuberculosis in penitentiary hospitals and in the general population of the former Soviet Union. Int J Tuberc Lung Dis 3:582–588

    PubMed  CAS  Google Scholar 

  29. Cox HS, Niemann S, Ismailov G et al (2007) Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance. Clin Infect Dis 44:1421–1427

    Article  PubMed  CAS  Google Scholar 

  30. Kuwabara K, Tsuchiya T (2007) Clinical features and treatment history of clarithromycin resistance in M. avium-intracellulare complex pulmonary disease patients. J Jap Respir Soc 45:587–592

    Google Scholar 

  31. Kuwabara K, Watanabe Y, Wada K et al (2004) Relations between clinical subtypes of Mycobacterium avium pulmonary disease and polyclonal infections detected by IS1245 based restriction fragment length polymorphism analysis. Kekkaku 79:39–46

    PubMed  CAS  Google Scholar 

  32. Zhang Y, Yew WW (2009) Mechanisms of drug resistance in Mycobacterium tuberculosis. Int J Tuberc Lung Dis 13:1320–1330

    PubMed  CAS  Google Scholar 

  33. Takiff HE, Salazar L, Guerrero C et al (1994) Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob Agents Chemother 38:773–780

    PubMed  CAS  Google Scholar 

  34. Meier A, Kirschner P, Springer B et al (1994) Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare. Antimicrob Agents Chemother 38:381–384

    PubMed  CAS  Google Scholar 

  35. Belanger AE, Besra GS, Ford ME et al (1996) The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc Natl Acad Sci USA 93:11919–11924

    Article  PubMed  CAS  Google Scholar 

  36. Hegde SS, Vetting MW, Roderick SL (2005) A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 308:1480–1483

    Article  PubMed  CAS  Google Scholar 

  37. Pasca MR, Guglierame P, Arcesi F et al (2004) Rv2686c-Rv2687c-Rv2688c, an ABC fluoroquinolone efflux pump in Mycobacterium tuberculosis. Antimicrob Agents Chemother 48:3175–3178

    Article  PubMed  CAS  Google Scholar 

  38. Sharma K, Gupta M, Krupa A et al (2006) EmbR, a regulatory protein with ATPase activity, is a substrate of multiple serine/threonine kinases and phosphatase in Mycobacterium tuberculosis. FEBS J 273:2711–2721

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported in part by a grant (18590850) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. We thank Taisho-Toyama Pharmaceutical Co., Daiichi Sankyo Co., Pfizer Japan Inc., Shionogi Pharmaceutical Co., and Kyorin Pharmaceutical Co. for providing antimicrobial drugs used in this study. We thank Ms. S. Yamabe for her kind assistance with this study.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo, Japan

    Y. Tatano, C. Sano, K. Yasumoto, T. Shimizu & H. Tomioka

  2. Kobe Women’s University, Kobe, Japan

    K. Sato

  3. National Institute of Animal Health, Tsukuba, Japan

    K. Nishimori

  4. Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan

    T. Matsumoto

  5. National Hospital Organization Matsue Medical Center, Matsue, Japan

    S. Yano & H. Takeyama

Authors
  1. Y. Tatano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Sano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Yasumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Nishimori
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H. Takeyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. H. Tomioka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Tomioka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tatano, Y., Sano, C., Yasumoto, K. et al. Correlation between variable-number tandem-repeat-based genotypes and drug susceptibility in Mycobacterium avium isolates. Eur J Clin Microbiol Infect Dis 31, 445–454 (2012). https://doi.org/10.1007/s10096-011-1326-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-011-1326-7

Keywords

Search

Navigation