Characterization of the Catalase-Peroxidase Gene (katG) and inhA Locus in Isoniazid-Resistant and -Susceptible Strains of Mycobacterium tuberculosis by Automated DNA Sequencing: Restricted Array of Mutations Associated with Drug Resistance

The catalase-peroxidase gene (katG) and a two-genelocus (inhA) containing mutations associated with resistance to isoniazid in Mycobacterium tuberculosis were sequenced in 34 resistant and 12 susceptible strains. Virtually all resistant organisms had amino acid changes in KatG or nucleotide substitu...

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Veröffentlicht in:The Journal of infectious diseases 1996-01, Vol.173 (1), p.196-202
Hauptverfasser: Musser, James M., Kapur, Vivek, Williams, Diana L., Kreiswirth, Barry N., van Soolingen, Dick, van Embden, Jan D. A.
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container_end_page 202
container_issue 1
container_start_page 196
container_title The Journal of infectious diseases
container_volume 173
creator Musser, James M.
Kapur, Vivek
Williams, Diana L.
Kreiswirth, Barry N.
van Soolingen, Dick
van Embden, Jan D. A.
description The catalase-peroxidase gene (katG) and a two-genelocus (inhA) containing mutations associated with resistance to isoniazid in Mycobacterium tuberculosis were sequenced in 34 resistant and 12 susceptible strains. Virtually all resistant organisms had amino acid changes in KatG or nucleotide substitutions upstream of inhA. A region of katG encoding two amino acids frequently altered in resistant strains (residues Ser31S and Arg463) and the inhA locus were sequenced in 10 susceptible and 51 isoniazid-resistant isolates from the Netherlands. Most (84%) of the resistant isolates had mutations in katG or the inhA locus or lacked katG. Together, ∼75% of isoniazid-resistant isolates had replacements at amino acids 315 or 463 in KatG or nucleotide substitutions upstream of inhA. All 16 strains of Mycobacterium bovis and Mycobacterium microti studied had Leu463 rather than Arg463in KatG, an observation consistent with the hypothesis that Leu463is the ancestral condition in M. tuberculosis.
doi_str_mv 10.1093/infdis/173.1.196
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A.</creatorcontrib><title>Characterization of the Catalase-Peroxidase Gene (katG) and inhA Locus in Isoniazid-Resistant and -Susceptible Strains of Mycobacterium tuberculosis by Automated DNA Sequencing: Restricted Array of Mutations Associated with Drug Resistance</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>The catalase-peroxidase gene (katG) and a two-genelocus (inhA) containing mutations associated with resistance to isoniazid in Mycobacterium tuberculosis were sequenced in 34 resistant and 12 susceptible strains. Virtually all resistant organisms had amino acid changes in KatG or nucleotide substitutions upstream of inhA. A region of katG encoding two amino acids frequently altered in resistant strains (residues Ser31S and Arg463) and the inhA locus were sequenced in 10 susceptible and 51 isoniazid-resistant isolates from the Netherlands. 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A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of the Catalase-Peroxidase Gene (katG) and inhA Locus in Isoniazid-Resistant and -Susceptible Strains of Mycobacterium tuberculosis by Automated DNA Sequencing: Restricted Array of Mutations Associated with Drug Resistance</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>1996-01</date><risdate>1996</risdate><volume>173</volume><issue>1</issue><spage>196</spage><epage>202</epage><pages>196-202</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>The catalase-peroxidase gene (katG) and a two-genelocus (inhA) containing mutations associated with resistance to isoniazid in Mycobacterium tuberculosis were sequenced in 34 resistant and 12 susceptible strains. Virtually all resistant organisms had amino acid changes in KatG or nucleotide substitutions upstream of inhA. 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subjects Amino Acid Sequence
Amino acids
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - pharmacology
Bacterial Proteins - genetics
Base Sequence
Biological and medical sciences
Catalase - genetics
Codons
DNA
DNA, Bacterial - analysis
Drug Resistance, Microbial - genetics
Genes, Bacterial
Genetic loci
Genetic mutation
Genetic variation
Humans
Isoniazid - pharmacology
Medical sciences
Molecular Sequence Data
Mutation
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - enzymology
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - isolation & purification
Nucleotides
Oxidoreductases
Peroxidase - genetics
Peroxidases - genetics
Pharmacology. Drug treatments
Sequence Analysis, DNA - methods
Sequencing
Tuberculosis
Tuberculosis - microbiology
title Characterization of the Catalase-Peroxidase Gene (katG) and inhA Locus in Isoniazid-Resistant and -Susceptible Strains of Mycobacterium tuberculosis by Automated DNA Sequencing: Restricted Array of Mutations Associated with Drug Resistance
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