Recombinant Mycobacterium tuberculosis KatG(S315T) Is a Competent Catalase-Peroxidase with Reduced Activity toward Isoniazid

The presence of KatG(S315T), a mutation frequently detected in clinical isolates of Mycobacterium tuberculosis, has been associated with loss of catalase-peroxidase activity and resistance to isoniazid therapy. Wild-type KatG and KatG(S315T) were expressed in a heterologous host (Escherichia coli) a...

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Veröffentlicht in:The Journal of infectious diseases 1997-09, Vol.176 (3), p.722-727
Hauptverfasser: Wengenack, Nancy L., Uhl, James R., St. Amand, Allison L., Tomlinson, Andy J., Benson, Linda M., Naylor, Stephen, Kline, Bruce C., Cockerill, Frank R., Rusnak, Frank
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container_end_page 727
container_issue 3
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container_title The Journal of infectious diseases
container_volume 176
creator Wengenack, Nancy L.
Uhl, James R.
St. Amand, Allison L.
Tomlinson, Andy J.
Benson, Linda M.
Naylor, Stephen
Kline, Bruce C.
Cockerill, Frank R.
Rusnak, Frank
description The presence of KatG(S315T), a mutation frequently detected in clinical isolates of Mycobacterium tuberculosis, has been associated with loss of catalase-peroxidase activity and resistance to isoniazid therapy. Wild-type KatG and KatG(S315T) were expressed in a heterologous host (Escherichia coli) and purified to homogeneity, and enzymatic activity was measured. The catalase activity for KatG(S315T) was reduced 6-fold, and its peroxidase activity was decreased
doi_str_mv 10.1086/514096
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Wild-type KatG and KatG(S315T) were expressed in a heterologous host (Escherichia coli) and purified to homogeneity, and enzymatic activity was measured. The catalase activity for KatG(S315T) was reduced 6-fold, and its peroxidase activity was decreased &lt;2-fold, compared with the activities for wild-type KatG. Pyridine hemochrome analysis demonstrated 1.1 ± 0.1 hemes/subunit for wild-type KatG and 0.9 ± 0.1 hemes/subunit for KatG(S315T), indicating that the difference in enzymatic activity is not the result of incomplete heme cofactor incorporation in KatG(S315T). High-performance liquid chromatography analysis showed that wild-type KatG was more efficient than KatG(S315T) at converting isoniazid to isonicotinic acid. 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Wild-type KatG and KatG(S315T) were expressed in a heterologous host (Escherichia coli) and purified to homogeneity, and enzymatic activity was measured. The catalase activity for KatG(S315T) was reduced 6-fold, and its peroxidase activity was decreased &lt;2-fold, compared with the activities for wild-type KatG. Pyridine hemochrome analysis demonstrated 1.1 ± 0.1 hemes/subunit for wild-type KatG and 0.9 ± 0.1 hemes/subunit for KatG(S315T), indicating that the difference in enzymatic activity is not the result of incomplete heme cofactor incorporation in KatG(S315T). High-performance liquid chromatography analysis showed that wild-type KatG was more efficient than KatG(S315T) at converting isoniazid to isonicotinic acid. 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Psychology</topic><topic>Genetic mutation</topic><topic>Infectious diseases</topic><topic>Isoniazid - metabolism</topic><topic>Major Articles</topic><topic>Mass spectroscopy</topic><topic>Microbiology</topic><topic>Molecular ions</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - drug effects</topic><topic>Mycobacterium tuberculosis - enzymology</topic><topic>Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains</topic><topic>Peroxidases - biosynthesis</topic><topic>Peroxidases - genetics</topic><topic>Peroxidases - isolation &amp; purification</topic><topic>Peroxidases - metabolism</topic><topic>Plasmids</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - isolation &amp; purification</topic><topic>Recombinant Proteins - metabolism</topic><topic>Tuberculosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wengenack, Nancy L.</creatorcontrib><creatorcontrib>Uhl, James R.</creatorcontrib><creatorcontrib>St. Amand, Allison L.</creatorcontrib><creatorcontrib>Tomlinson, Andy J.</creatorcontrib><creatorcontrib>Benson, Linda M.</creatorcontrib><creatorcontrib>Naylor, Stephen</creatorcontrib><creatorcontrib>Kline, Bruce C.</creatorcontrib><creatorcontrib>Cockerill, Frank R.</creatorcontrib><creatorcontrib>Rusnak, Frank</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wengenack, Nancy L.</au><au>Uhl, James R.</au><au>St. Amand, Allison L.</au><au>Tomlinson, Andy J.</au><au>Benson, Linda M.</au><au>Naylor, Stephen</au><au>Kline, Bruce C.</au><au>Cockerill, Frank R.</au><au>Rusnak, Frank</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recombinant Mycobacterium tuberculosis KatG(S315T) Is a Competent Catalase-Peroxidase with Reduced Activity toward Isoniazid</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>1997-09-01</date><risdate>1997</risdate><volume>176</volume><issue>3</issue><spage>722</spage><epage>727</epage><pages>722-727</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>The presence of KatG(S315T), a mutation frequently detected in clinical isolates of Mycobacterium tuberculosis, has been associated with loss of catalase-peroxidase activity and resistance to isoniazid therapy. Wild-type KatG and KatG(S315T) were expressed in a heterologous host (Escherichia coli) and purified to homogeneity, and enzymatic activity was measured. The catalase activity for KatG(S315T) was reduced 6-fold, and its peroxidase activity was decreased &lt;2-fold, compared with the activities for wild-type KatG. Pyridine hemochrome analysis demonstrated 1.1 ± 0.1 hemes/subunit for wild-type KatG and 0.9 ± 0.1 hemes/subunit for KatG(S315T), indicating that the difference in enzymatic activity is not the result of incomplete heme cofactor incorporation in KatG(S315T). High-performance liquid chromatography analysis showed that wild-type KatG was more efficient than KatG(S315T) at converting isoniazid to isonicotinic acid. These results demonstrate that KatG(S315T), as expressed in E. coli, is a competent catalase-peroxidase that exhibits a reduced ability to metabolize isoniazid.</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>9291321</pmid><doi>10.1086/514096</doi><tpages>6</tpages></addata></record>
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source Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); MEDLINE
subjects Amino Acid Sequence
Bacterial Proteins
Bacteriology
Biochemistry
Biological and medical sciences
Catalase - metabolism
Chromatography, High Pressure Liquid
Enzymes
Escherichia coli
Fundamental and applied biological sciences. Psychology
Genetic mutation
Infectious diseases
Isoniazid - metabolism
Major Articles
Mass spectroscopy
Microbiology
Molecular ions
Molecular Sequence Data
Mutagenesis, Site-Directed
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - enzymology
Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains
Peroxidases - biosynthesis
Peroxidases - genetics
Peroxidases - isolation & purification
Peroxidases - metabolism
Plasmids
Recombinant Proteins - genetics
Recombinant Proteins - isolation & purification
Recombinant Proteins - metabolism
Tuberculosis
title Recombinant Mycobacterium tuberculosis KatG(S315T) Is a Competent Catalase-Peroxidase with Reduced Activity toward Isoniazid
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