Molecular genetics of Mycobacterium tuberculosis resistant to aminoglycosides and cyclic peptide capreomycin antibiotics in Korea

  • Hum Nath Jnawali
  • Heekyung Yoo
  • Sungweon Ryoo
  • Kwang-Jun Lee
  • Bum-Joon Kim
  • Won-Jung Koh
  • Chang-Ki Kim
  • Hee-Jin Kim
  • Young Kil Park
Original Paper

Abstract

Aminoglycosides are key drugs for the treatment of multidrug-resistant tuberculosis. A total of 97 extensively drug-resistant (XDR) and 29 pan-susceptible Mycobacterium tuberculosis isolates from Korean tuberculosis patients were analyzed to characterize mutations within the rrs, rpsL, gidB, eis and tlyA genes. Thirty (56.6 %) of the 53 streptomycin (STR)-resistant strains had a rpsL mutation and eight strains (15.1 %) had a rrs (514 or 908 site) mutation, whereas 11 (20.8 %) of the 53 STR-resistant strains had a gidB mutation without rpsL or either rrs mutation. Most of the gidB mutations conferred low-level STR resistance, and 22 of these mutations were novel. Mutation at position 1401 in rrs lead to resistance to kanamycin (80/95 = 84.2 %; KAN), amikacin (80/87 = 92.0 %; AMK), and capreomycin (74/86 = 86.0 %; CAP). In this study, 13.7 % (13/95) of KAN-resistant strains showed eis mutations, including 4 kinds of novel mutations. Isolates with eis structural gene mutations were cross-resistant to STR, KAN, CAP, and AMK. Here, 5.8 % (5/86) of the CAP-resistant strains harbored a tlyA mutation that included 3 different novel point mutations. Detection of the A1401G mutation appeared to be 100 % specific for the detection of resistance to KAN and AMK. These data establish the presence of phenotypic XDR strains using molecular profiling and are helpful to understanding of aminoglycoside resistance at the molecular level.

Keywords

Mycobacterium tuberculosis Aminoglycosides Mutations Extensively drug-resistant TB Pan-susceptible Polymerase chain reaction 

Supplementary material

11274_2013_1256_MOESM1_ESM.xlsx (22 kb)
Supplementary material 1 (XLSX 22 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Hum Nath Jnawali
    • 1
  • Heekyung Yoo
    • 1
  • Sungweon Ryoo
    • 1
  • Kwang-Jun Lee
    • 2
  • Bum-Joon Kim
    • 3
  • Won-Jung Koh
    • 4
  • Chang-Ki Kim
    • 1
  • Hee-Jin Kim
    • 1
  • Young Kil Park
    • 1
  1. 1.Department of Research and DevelopmentKorean Institute of TuberculosisCheongwongunRepublic of Korea
  2. 2.Center for Infectious Diseases, NIH, KCDCOsongupRepublic of Korea
  3. 3.Microbiology and Immunology, College of MedicineSeoul National UnversitySeoulRepublic of Korea
  4. 4.Division of Pulmonary and Critical Care Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea

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