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 |
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container_title | The Journal of infectious diseases |
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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 <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.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/514096</identifier><identifier>PMID: 9291321</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject>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</subject><ispartof>The Journal of infectious diseases, 1997-09, Vol.176 (3), p.722-727</ispartof><rights>Copyright 1997 The University of Chicago</rights><rights>1997 INIST-CNRS</rights><rights>Copyright University of Chicago, acting through its Press Sep 1997</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-80d12452903943eb85b55596c64c962d19dbb75dab64c02e515c2207679fa8193</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30107353$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30107353$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2824482$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9291321$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Recombinant Mycobacterium tuberculosis KatG(S315T) Is a Competent Catalase-Peroxidase with Reduced Activity toward Isoniazid</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><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 <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.</description><subject>Amino Acid Sequence</subject><subject>Bacterial Proteins</subject><subject>Bacteriology</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Catalase - metabolism</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Enzymes</subject><subject>Escherichia coli</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic mutation</subject><subject>Infectious diseases</subject><subject>Isoniazid - metabolism</subject><subject>Major Articles</subject><subject>Mass spectroscopy</subject><subject>Microbiology</subject><subject>Molecular ions</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - drug effects</subject><subject>Mycobacterium tuberculosis - enzymology</subject><subject>Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains</subject><subject>Peroxidases - biosynthesis</subject><subject>Peroxidases - genetics</subject><subject>Peroxidases - isolation & purification</subject><subject>Peroxidases - metabolism</subject><subject>Plasmids</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - isolation & purification</subject><subject>Recombinant Proteins - metabolism</subject><subject>Tuberculosis</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkV1rFDEUhoNY6rbqPxCClGIvRvMxySSXddHdYkVZVxRvQibJYtaZyZpkbLf0xxvZZQtenXCe57yEcwB4jtFrjAR_w3CNJH8EJpjRpuIc08dgghAhFRZSPgEnKa0RQjXlzTE4lkRiSvAE3C-cCX3rBz1k-HFrQqtNdtGPPcxj66IZu5B8gh90nr36QjFbXsCrBDWchn7jsitTU511p5OrPrsYbr0tT3jj80-4cHY0zsJLk_0fn7cwhxsdbZkPg9d33j4FRyvdJfdsX0_B1_fvltN5df1pdjW9vK5MTXCuBLKY1IxIRGVNXStYyxiT3PDaSE4slrZtG2Z1WxqIOIaZIQQ1vJErLbCkp-B8l7uJ4ffoUla9T8Z1nR5cGJPCHCOJRV3El_-J6zDGofxNEULLyhgRD2kmhpSiW6lN9L2OW4WR-ncLtbtFEV_s08a2d_ag7Zdf-Nme62R0t4p6MD4dNCJIXQvyELNOOcQDpgijhjJaeLXjPmV3e-A6_lK8oQ1T8-8_1HzRiLff5Ewt6V_6YadB</recordid><startdate>19970901</startdate><enddate>19970901</enddate><creator>Wengenack, Nancy L.</creator><creator>Uhl, James R.</creator><creator>St. Amand, Allison L.</creator><creator>Tomlinson, Andy J.</creator><creator>Benson, Linda M.</creator><creator>Naylor, Stephen</creator><creator>Kline, Bruce C.</creator><creator>Cockerill, Frank R.</creator><creator>Rusnak, Frank</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7QL</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>19970901</creationdate><title>Recombinant Mycobacterium tuberculosis KatG(S315T) Is a Competent Catalase-Peroxidase with Reduced Activity toward Isoniazid</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-80d12452903943eb85b55596c64c962d19dbb75dab64c02e515c2207679fa8193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Amino Acid Sequence</topic><topic>Bacterial Proteins</topic><topic>Bacteriology</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Catalase - metabolism</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Enzymes</topic><topic>Escherichia coli</topic><topic>Fundamental and applied biological sciences. 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 & purification</topic><topic>Peroxidases - metabolism</topic><topic>Plasmids</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - isolation & 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 & Medical Complete (Alumni)</collection><collection>Nursing & 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 <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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