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Mycobacteriology and Aerobic Actinomycetes

Detection of Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis Isolates from China

Min Zhang, Jun Yue, Yan-ping Yang, Hong-mei Zhang, Jian-qiang Lei, Rui-liang Jin, Xue-lian Zhang, Hong-hai Wang
Min Zhang
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University
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Jun Yue
2Shanghai Pneumology Hospital, Shanghai 200433, People's Republic of China
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Yan-ping Yang
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University
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Hong-mei Zhang
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University
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Jian-qiang Lei
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University
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Rui-liang Jin
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University
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Xue-lian Zhang
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University
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Hong-hai Wang
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University
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  • For correspondence: hhwang@fudan.edu.cn
DOI: 10.1128/JCM.43.11.5477-5482.2005
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Tables

  • TABLE 1.

    katG double mutations in 87 INH-resistant M. tuberculosis isolates from China

    Nucleotide no. for the first mutation in katGAmino acidSecond mutation in katGNo. (%) of isolates with mutationINH MIC range (μg/ml)Additional mutation(s) (no. of isolates)
    Nucleotide no.Amino acid
    G→C at position 944Ser315ThrG→T at position 1388Arg463Leu13 (14.9)1->256 oxyR-ahpC (2), inhA promoter (2), iniA (1)
    G→A at position 944Ser315AsnG→T at position 1388Arg463Leu1 (1.1)16None
    G→C at position 944Ser315ThrG→C at position 2053Gly685Arg1 (1.1)2None
    G→C at position 944Ser315ThrA insertion at position 1329Frameshift1 (1.1)64 oxyR-ahpC (1)
    G→T at position 1388Arg463LeuG→T at position 1471Gly491Cys2 (2.3)4-8 inhA (1)
    G→T at position 1388Arg463LeuCG→TA at position 1543→1544Arg515Tyr1 (1.1)8None
    G→T at position 1388Arg463Leu64-bp insertion at position 15591 (1.1)>256 oxyR-ahpC (1), efpA (1)
  • TABLE 2.

    Nonsynonymous mutations in INH-susceptible and -resistant M. tuberculosis from China

    Gene or gene regionNonsynonymous mutationNo. of INH-susceptible isolates (n = 50)No. of INH-resistant isolates with indicated INH MIC range (μg/ml)
    0.2 ≤ MIC < 1 (n = 24)1 ≤ MIC < 10 (n = 48)MIC ≥ 10 (n = 15)
    furA Ser50011
    katG Completed deletion0002
    Frameshift0012
    Trp90Stop0010
    Ser31509389
    Arg463011177
    Gly4910020
    Arg5150010
    Gly6850010
    inhA promoter−15 C→T0282
    −17 G→T0001
    inhA Ile210011
    Ile2580020
    oxyR-ahpC −9 G→A0011
    −10 C→T0010
    −12 C→T0002
    −15 C→T0010
    −39 C→T0013
    −48 G→A0001
    kasA Met770001
    Leu2450010
    Gly2690101
    Gly3128231
    Ser3412201
    Rv0340Thr1434110
    Gly1495000
    Val1630010
    iniB Frameshift0110
    Gly1922211
    iniA Arg5370101
    His4813211
    iniC Frameshift0011
    efpA Ile734321
    Glu5200001
  • TABLE 3.

    INH-resistant M. tuberculosis isolates with mutations in two or more genes

    No. of isolatesMIC range (μg/ml)Mutation(s)a
    furAkatGinhA promoterinhAoxyR-ahpCkasARv0340iniBiniAiniCefpA
    141559 C Delb,e−15 C→T
    1161311 T InscM771
    132Del−9 G→A
    1>256Del−12 C→T
    50.5-32S315T−15 C→T
    11S315TI21T198 T Inse
    12S315T−9 G→A
    12S315T−39 C→T
    12S315T79 T Ins
    116S315T−17 G→T
    116S315TI21V
    116S315TG269S98 A Inse
    10.5R463L
    11R463LL245R
    12R463LI258TeG269SR537H
    14R463LV1631
    116R463L−15 C→T
    116S5PR463L−39 C→Te−39 C→T
    21-2S315T; R463L−15 C→T
    12S315T; R463L−10 C→T
    132S315T; R463L−48 G→AR537H
    164S315T; 1329 A−39 C→T
    Ins
    1>256R463L; 1559 Ins of 64 bpd,e−12 C→T;     −39 C→TE520Ve
    14R463L; G491CeI258Te
    12S5P−15 C→T
    • ↵ a Amino acid abbreviations: S, Ser; T, Thr; R, Arg; L, Leu; P, Pro; G, Gly; C, Cys; I, Ile; V, Val; M, Met; H, His; E, Glu. Nucleotide abbreviations: A, adenine; C, cytosine; G, guanine, T, thymidine.

    • ↵ b Deletion (Del) of nucleotide C at position 1559.

    • ↵ c Insertion (Ins) of nucleotide T at position 1311.

    • ↵ d Insertion (64 bp) at position 1559.

    • ↵ e Novel mutation.

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Detection of Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis Isolates from China
Min Zhang, Jun Yue, Yan-ping Yang, Hong-mei Zhang, Jian-qiang Lei, Rui-liang Jin, Xue-lian Zhang, Hong-hai Wang
Journal of Clinical Microbiology Nov 2005, 43 (11) 5477-5482; DOI: 10.1128/JCM.43.11.5477-5482.2005

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Detection of Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis Isolates from China
Min Zhang, Jun Yue, Yan-ping Yang, Hong-mei Zhang, Jian-qiang Lei, Rui-liang Jin, Xue-lian Zhang, Hong-hai Wang
Journal of Clinical Microbiology Nov 2005, 43 (11) 5477-5482; DOI: 10.1128/JCM.43.11.5477-5482.2005
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KEYWORDS

Antitubercular Agents
Genes, Bacterial
isoniazid
Mycobacterium tuberculosis

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