A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets in Corynebacterium pseudotuberculosis and other CMN Group of Human Pathogens
Identifieur interne : 001044 ( Istex/Corpus ); précédent : 001043; suivant : 001045A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets in Corynebacterium pseudotuberculosis and other CMN Group of Human Pathogens
Auteurs : Debmalya Barh ; Neha Jain ; Sandeep Tiwari ; Bibhu Prasad Parida ; Vivian D Fonseca ; Liwei Li ; Amjad Ali ; Anderson Rodrigues Santos ; Luís Carlos Guimarães ; Siomar De Castro Soares ; Anderson Miyoshi ; Atanu Bhattacharjee ; Amarendra Narayan Misra ; Artur Silva ; Anil Kumar ; Vasco AzevedoSource :
- Chemical Biology & Drug Design [ 1747-0277 ] ; 2011-07.
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Abstract
Caseous lymphadenitis is a chronic goat and sheep disease caused by Corynebacterium pseudotuberculosis (Cp) that accounts for a huge economic loss worldwide. Proper vaccination or medication is not available because of the lack of understanding of molecular biology of the pathogen. In a recent approach, four Cp (CpFrc41, Cp1002, CpC231, and CpI‐19) genomes were sequenced to elucidate the molecular pathology of the bacteria. In this study, using these four genome sequences along with other eight genomes (total 12 genomes) and a novel subtractive genomics approach (first time ever applied to a veterinary pathogen), we identified potential conserved common drug and vaccine targets of these four Cp strains along with other Corybacterium, Mycobacterium and Nocardia (CMN) group of human pathogens (Corynebacterium diphtheriae and Mycobacterium tuberculosis) considering goat, sheep, bovine, horse, and human as the most affected hosts. The minimal genome of Cp1002 was found to consist of 724 genes, and 20 conserved common targets (to all Cp strains as well as CMN group of pathogens) from various metabolic pathways (13 from host‐pathogen common and seven from pathogen’s unique pathways) are potential targets irrespective of all hosts considered. ubiA from host‐pathogen common pathway and an ABC‐like transporter from unique pathways may serve dual (drug and vaccine) targets. Two Corynebacterium‐specific (mscL and resB) and one broad‐spectrum (rpmB) novel targets were also identified. Strain‐specific targets are also discussed. Six important targets were subjected to virtual screening, and one compound was found to be potent enough to render two targets (cdc and nrdL). We are currently validating all identified targets and lead compounds.
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DOI: 10.1111/j.1747-0285.2011.01118.x
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Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</mods:affiliation></affiliation></author><author><name sortKey="D Fonseca, Vivian" sort="D Fonseca, Vivian" uniqKey="D Fonseca V" first="Vivian" last="D Fonseca">Vivian D Fonseca</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Li, Liwei" sort="Li, Liwei" uniqKey="Li L" first="Liwei" last="Li">Liwei Li</name><affiliation><mods:affiliation>Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA</mods:affiliation></affiliation></author><author><name sortKey="Ali, Amjad" sort="Ali, Amjad" uniqKey="Ali A" first="Amjad" last="Ali">Amjad Ali</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Santos, Anderson Rodrigues" sort="Santos, Anderson Rodrigues" uniqKey="Santos A" first="Anderson Rodrigues" last="Santos">Anderson Rodrigues Santos</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Guimaraes, Luis Carlos" sort="Guimaraes, Luis Carlos" uniqKey="Guimaraes L" first="Luís Carlos" last="Guimarães">Luís Carlos Guimarães</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="De Castro Soares, Siomar" sort="De Castro Soares, Siomar" uniqKey="De Castro Soares S" first="Siomar" last="De Castro Soares">Siomar De Castro Soares</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Miyoshi, Anderson" sort="Miyoshi, Anderson" uniqKey="Miyoshi A" first="Anderson" last="Miyoshi">Anderson Miyoshi</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Bhattacharjee, Atanu" sort="Bhattacharjee, Atanu" uniqKey="Bhattacharjee A" first="Atanu" last="Bhattacharjee">Atanu Bhattacharjee</name><affiliation><mods:affiliation>Department of Biotechnology and Bioinformatics, Bioinformatics Laboratory, North Eastern Hill University, Shillong, India</mods:affiliation></affiliation></author><author><name sortKey="Misra, Amarendra Narayan" sort="Misra, Amarendra Narayan" uniqKey="Misra A" first="Amarendra Narayan" last="Misra">Amarendra Narayan Misra</name><affiliation><mods:affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</mods:affiliation></affiliation></author><author><name sortKey="Silva, Artur" sort="Silva, Artur" uniqKey="Silva A" first="Artur" last="Silva">Artur Silva</name><affiliation><mods:affiliation>Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém‐PA, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Kumar, Anil" sort="Kumar, Anil" uniqKey="Kumar A" first="Anil" last="Kumar">Anil Kumar</name><affiliation><mods:affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</mods:affiliation></affiliation></author><author><name sortKey="Azevedo, Vasco" sort="Azevedo, Vasco" uniqKey="Azevedo V" first="Vasco" last="Azevedo">Vasco Azevedo</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:E90778391939DFC6D4731CC1D10B195633EDFA80</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1111/j.1747-0285.2011.01118.x</idno><idno type="url">https://api.istex.fr/document/E90778391939DFC6D4731CC1D10B195633EDFA80/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001044</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001044</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets in Corynebacterium pseudotuberculosis and other CMN Group of Human Pathogens</title><author><name sortKey="Barh, Debmalya" sort="Barh, Debmalya" uniqKey="Barh D" first="Debmalya" last="Barh">Debmalya Barh</name><affiliation><mods:affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</mods:affiliation></affiliation></author><author><name sortKey="Jain, Neha" sort="Jain, Neha" uniqKey="Jain N" first="Neha" last="Jain">Neha Jain</name><affiliation><mods:affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</mods:affiliation></affiliation><affiliation><mods:affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</mods:affiliation></affiliation></author><author><name sortKey="Tiwari, Sandeep" sort="Tiwari, Sandeep" uniqKey="Tiwari S" first="Sandeep" last="Tiwari">Sandeep Tiwari</name><affiliation><mods:affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</mods:affiliation></affiliation><affiliation><mods:affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</mods:affiliation></affiliation></author><author><name sortKey="Parida, Bibhu Prasad" sort="Parida, Bibhu Prasad" uniqKey="Parida B" first="Bibhu Prasad" last="Parida">Bibhu Prasad Parida</name><affiliation><mods:affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</mods:affiliation></affiliation></author><author><name sortKey="D Fonseca, Vivian" sort="D Fonseca, Vivian" uniqKey="D Fonseca V" first="Vivian" last="D Fonseca">Vivian D Fonseca</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Li, Liwei" sort="Li, Liwei" uniqKey="Li L" first="Liwei" last="Li">Liwei Li</name><affiliation><mods:affiliation>Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA</mods:affiliation></affiliation></author><author><name sortKey="Ali, Amjad" sort="Ali, Amjad" uniqKey="Ali A" first="Amjad" last="Ali">Amjad Ali</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Santos, Anderson Rodrigues" sort="Santos, Anderson Rodrigues" uniqKey="Santos A" first="Anderson Rodrigues" last="Santos">Anderson Rodrigues Santos</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Guimaraes, Luis Carlos" sort="Guimaraes, Luis Carlos" uniqKey="Guimaraes L" first="Luís Carlos" last="Guimarães">Luís Carlos Guimarães</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="De Castro Soares, Siomar" sort="De Castro Soares, Siomar" uniqKey="De Castro Soares S" first="Siomar" last="De Castro Soares">Siomar De Castro Soares</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Miyoshi, Anderson" sort="Miyoshi, Anderson" uniqKey="Miyoshi A" first="Anderson" last="Miyoshi">Anderson Miyoshi</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Bhattacharjee, Atanu" sort="Bhattacharjee, Atanu" uniqKey="Bhattacharjee A" first="Atanu" last="Bhattacharjee">Atanu Bhattacharjee</name><affiliation><mods:affiliation>Department of Biotechnology and Bioinformatics, Bioinformatics Laboratory, North Eastern Hill University, Shillong, India</mods:affiliation></affiliation></author><author><name sortKey="Misra, Amarendra Narayan" sort="Misra, Amarendra Narayan" uniqKey="Misra A" first="Amarendra Narayan" last="Misra">Amarendra Narayan Misra</name><affiliation><mods:affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</mods:affiliation></affiliation></author><author><name sortKey="Silva, Artur" sort="Silva, Artur" uniqKey="Silva A" first="Artur" last="Silva">Artur Silva</name><affiliation><mods:affiliation>Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém‐PA, Brazil</mods:affiliation></affiliation></author><author><name sortKey="Kumar, Anil" sort="Kumar, Anil" uniqKey="Kumar A" first="Anil" last="Kumar">Anil Kumar</name><affiliation><mods:affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</mods:affiliation></affiliation></author><author><name sortKey="Azevedo, Vasco" sort="Azevedo, Vasco" uniqKey="Azevedo V" first="Vasco" last="Azevedo">Vasco Azevedo</name><affiliation><mods:affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Chemical Biology & Drug Design</title><idno type="ISSN">1747-0277</idno><idno type="eISSN">1747-0285</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2011-07">2011-07</date><biblScope unit="volume">78</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="73">73</biblScope><biblScope unit="page" to="84">84</biblScope></imprint><idno type="ISSN">1747-0277</idno></series><idno type="istex">E90778391939DFC6D4731CC1D10B195633EDFA80</idno><idno type="DOI">10.1111/j.1747-0285.2011.01118.x</idno><idno type="ArticleID">CBDD1118</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1747-0277</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Corynebacterium pseudotuberculosis</term><term>drug and vaccine targets</term><term>minimal genome</term><term>subtractive genomics</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Caseous lymphadenitis is a chronic goat and sheep disease caused by Corynebacterium pseudotuberculosis (Cp) that accounts for a huge economic loss worldwide. Proper vaccination or medication is not available because of the lack of understanding of molecular biology of the pathogen. In a recent approach, four Cp (CpFrc41, Cp1002, CpC231, and CpI‐19) genomes were sequenced to elucidate the molecular pathology of the bacteria. In this study, using these four genome sequences along with other eight genomes (total 12 genomes) and a novel subtractive genomics approach (first time ever applied to a veterinary pathogen), we identified potential conserved common drug and vaccine targets of these four Cp strains along with other Corybacterium, Mycobacterium and Nocardia (CMN) group of human pathogens (Corynebacterium diphtheriae and Mycobacterium tuberculosis) considering goat, sheep, bovine, horse, and human as the most affected hosts. The minimal genome of Cp1002 was found to consist of 724 genes, and 20 conserved common targets (to all Cp strains as well as CMN group of pathogens) from various metabolic pathways (13 from host‐pathogen common and seven from pathogen’s unique pathways) are potential targets irrespective of all hosts considered. ubiA from host‐pathogen common pathway and an ABC‐like transporter from unique pathways may serve dual (drug and vaccine) targets. Two Corynebacterium‐specific (mscL and resB) and one broad‐spectrum (rpmB) novel targets were also identified. Strain‐specific targets are also discussed. Six important targets were subjected to virtual screening, and one compound was found to be potent enough to render two targets (cdc and nrdL). We are currently validating all identified targets and lead compounds.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Debmalya Barh</name><affiliations><json:string>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</json:string><json:string>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</json:string></affiliations></json:item><json:item><name>Neha Jain</name><affiliations><json:string>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</json:string><json:string>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</json:string></affiliations></json:item><json:item><name>Sandeep Tiwari</name><affiliations><json:string>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</json:string><json:string>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</json:string></affiliations></json:item><json:item><name>Bibhu Prasad Parida</name><affiliations><json:string>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</json:string><json:string>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</json:string></affiliations></json:item><json:item><name>Vivian D’Afonseca</name><affiliations><json:string>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</json:string></affiliations></json:item><json:item><name>Liwei Li</name><affiliations><json:string>Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA</json:string></affiliations></json:item><json:item><name>Amjad Ali</name><affiliations><json:string>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</json:string></affiliations></json:item><json:item><name>Anderson Rodrigues Santos</name><affiliations><json:string>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</json:string></affiliations></json:item><json:item><name>Luís Carlos Guimarães</name><affiliations><json:string>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</json:string></affiliations></json:item><json:item><name>Siomar de Castro Soares</name><affiliations><json:string>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</json:string></affiliations></json:item><json:item><name>Anderson Miyoshi</name><affiliations><json:string>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</json:string></affiliations></json:item><json:item><name>Atanu Bhattacharjee</name><affiliations><json:string>Department of Biotechnology and Bioinformatics, Bioinformatics Laboratory, North Eastern Hill University, Shillong, India</json:string></affiliations></json:item><json:item><name>Amarendra Narayan Misra</name><affiliations><json:string>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</json:string></affiliations></json:item><json:item><name>Artur Silva</name><affiliations><json:string>Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém‐PA, Brazil</json:string></affiliations></json:item><json:item><name>Anil Kumar</name><affiliations><json:string>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</json:string></affiliations></json:item><json:item><name>Vasco Azevedo</name><affiliations><json:string>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Corynebacterium pseudotuberculosis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>drug and vaccine targets</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>minimal genome</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>subtractive genomics</value></json:item></subject><articleId><json:string>CBDD1118</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Caseous lymphadenitis is a chronic goat and sheep disease caused by Corynebacterium pseudotuberculosis (Cp) that accounts for a huge economic loss worldwide. Proper vaccination or medication is not available because of the lack of understanding of molecular biology of the pathogen. In a recent approach, four Cp (CpFrc41, Cp1002, CpC231, and CpI‐19) genomes were sequenced to elucidate the molecular pathology of the bacteria. In this study, using these four genome sequences along with other eight genomes (total 12 genomes) and a novel subtractive genomics approach (first time ever applied to a veterinary pathogen), we identified potential conserved common drug and vaccine targets of these four Cp strains along with other Corybacterium, Mycobacterium and Nocardia (CMN) group of human pathogens (Corynebacterium diphtheriae and Mycobacterium tuberculosis) considering goat, sheep, bovine, horse, and human as the most affected hosts. The minimal genome of Cp1002 was found to consist of 724 genes, and 20 conserved common targets (to all Cp strains as well as CMN group of pathogens) from various metabolic pathways (13 from host‐pathogen common and seven from pathogen’s unique pathways) are potential targets irrespective of all hosts considered. ubiA from host‐pathogen common pathway and an ABC‐like transporter from unique pathways may serve dual (drug and vaccine) targets. Two Corynebacterium‐specific (mscL and resB) and one broad‐spectrum (rpmB) novel targets were also identified. Strain‐specific targets are also discussed. Six important targets were subjected to virtual screening, and one compound was found to be potent enough to render two targets (cdc and nrdL). We are currently validating all identified targets and lead compounds.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.276 x 782.362 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>4</keywordCount><abstractCharCount>1756</abstractCharCount><pdfWordCount>7791</pdfWordCount><pdfCharCount>49983</pdfCharCount><pdfPageCount>12</pdfPageCount><abstractWordCount>258</abstractWordCount></qualityIndicators><title>A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets in Corynebacterium pseudotuberculosis and other CMN Group of Human Pathogens</title><genre><json:string>article</json:string></genre><host><volume>78</volume><publisherId><json:string>CBDD</json:string></publisherId><pages><total>13</total><last>84</last><first>73</first></pages><issn><json:string>1747-0277</json:string></issn><issue>1</issue><subject><json:item><value>Research 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Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</affiliation><affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</affiliation></author><author xml:id="author-2"><persName><forename type="first">Neha</forename><surname>Jain</surname></persName><affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</affiliation><affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</affiliation></author><author xml:id="author-3"><persName><forename type="first">Sandeep</forename><surname>Tiwari</surname></persName><affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</affiliation><affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</affiliation></author><author xml:id="author-4"><persName><forename type="first">Bibhu Prasad</forename><surname>Parida</surname></persName><affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</affiliation><affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</affiliation></author><author xml:id="author-5"><persName><forename type="first">Vivian</forename><surname>D’Afonseca</surname></persName><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation></author><author xml:id="author-6"><persName><forename type="first">Liwei</forename><surname>Li</surname></persName><affiliation>Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA</affiliation></author><author xml:id="author-7"><persName><forename type="first">Amjad</forename><surname>Ali</surname></persName><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation></author><author xml:id="author-8"><persName><forename type="first">Anderson Rodrigues</forename><surname>Santos</surname></persName><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation></author><author xml:id="author-9"><persName><forename type="first">Luís Carlos</forename><surname>Guimarães</surname></persName><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation></author><author xml:id="author-10"><persName><forename type="first">Siomar</forename><surname>de Castro Soares</surname></persName><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation></author><author xml:id="author-11"><persName><forename type="first">Anderson</forename><surname>Miyoshi</surname></persName><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation></author><author xml:id="author-12"><persName><forename type="first">Atanu</forename><surname>Bhattacharjee</surname></persName><affiliation>Department of Biotechnology and Bioinformatics, Bioinformatics Laboratory, North Eastern Hill University, Shillong, India</affiliation></author><author xml:id="author-13"><persName><forename type="first">Amarendra Narayan</forename><surname>Misra</surname></persName><affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</affiliation></author><author xml:id="author-14"><persName><forename type="first">Artur</forename><surname>Silva</surname></persName><affiliation>Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém‐PA, Brazil</affiliation></author><author xml:id="author-15"><persName><forename type="first">Anil</forename><surname>Kumar</surname></persName><affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</affiliation></author><author xml:id="author-16"><persName><forename type="first">Vasco</forename><surname>Azevedo</surname></persName><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation></author></analytic><monogr><title level="j">Chemical Biology & Drug Design</title><idno type="pISSN">1747-0277</idno><idno type="eISSN">1747-0285</idno><idno type="DOI">10.1111/(ISSN)1747-0285</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2011-07"></date><biblScope unit="volume">78</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="73">73</biblScope><biblScope unit="page" to="84">84</biblScope></imprint></monogr><idno type="istex">E90778391939DFC6D4731CC1D10B195633EDFA80</idno><idno type="DOI">10.1111/j.1747-0285.2011.01118.x</idno><idno type="ArticleID">CBDD1118</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Caseous lymphadenitis is a chronic goat and sheep disease caused by Corynebacterium pseudotuberculosis (Cp) that accounts for a huge economic loss worldwide. Proper vaccination or medication is not available because of the lack of understanding of molecular biology of the pathogen. In a recent approach, four Cp (CpFrc41, Cp1002, CpC231, and CpI‐19) genomes were sequenced to elucidate the molecular pathology of the bacteria. In this study, using these four genome sequences along with other eight genomes (total 12 genomes) and a novel subtractive genomics approach (first time ever applied to a veterinary pathogen), we identified potential conserved common drug and vaccine targets of these four Cp strains along with other Corybacterium, Mycobacterium and Nocardia (CMN) group of human pathogens (Corynebacterium diphtheriae and Mycobacterium tuberculosis) considering goat, sheep, bovine, horse, and human as the most affected hosts. The minimal genome of Cp1002 was found to consist of 724 genes, and 20 conserved common targets (to all Cp strains as well as CMN group of pathogens) from various metabolic pathways (13 from host‐pathogen common and seven from pathogen’s unique pathways) are potential targets irrespective of all hosts considered. ubiA from host‐pathogen common pathway and an ABC‐like transporter from unique pathways may serve dual (drug and vaccine) targets. Two Corynebacterium‐specific (mscL and resB) and one broad‐spectrum (rpmB) novel targets were also identified. Strain‐specific targets are also discussed. Six important targets were subjected to virtual screening, and one compound was found to be potent enough to render two targets (cdc and nrdL). We are currently validating all identified targets and lead compounds.</p></abstract><abstract style="graphical"><p>Various metabolic pathway related common, conserved, novel, and dual targets (drug and vaccine) in C. diphtheriae, M. tuberculosis, and four C. pseudotuberculosis strains are identified using total 12 genomes (4 are newly sequenced) and a novel subtractive genomic approach. Applying virtual screening, one compound is selected that can render two different targets cdc and nrdL simultaneously</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>Corynebacterium pseudotuberculosis</term></item><item><term>drug and vaccine targets</term></item><item><term>minimal genome</term></item><item><term>subtractive genomics</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2011-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/E90778391939DFC6D4731CC1D10B195633EDFA80/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: 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2011</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="9" status="forIssue"><doi origin="wiley">10.1111/j.1747-0285.2011.01118.x</doi><idGroup><id type="unit" value="CBDD1118"></id></idGroup><countGroup><count type="pageTotal" number="13"></count></countGroup><titleGroup><title type="tocHeading1">Research Articles</title><title type="articleCategory">Research Article</title></titleGroup><copyright>© 2011 John Wiley & Sons A/S</copyright><eventGroup><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.5 mode:FullText" date="2011-06-13"></event><event type="publishedOnlineAccepted" date="2011-03-28"></event><event type="publishedOnlineEarlyUnpaginated" date="2011-05-25"></event><event type="firstOnline" date="2011-05-25"></event><event type="publishedOnlineFinalForm" date="2011-06-13"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-08"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-15"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="73">73</numbering><numbering type="pageLast" number="84">84</numbering></numberingGroup><correspondenceTo><i> Corresponding author: Debmalya Barh, </i><email>dr.barh@gmail.com</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:CBDD.CBDD1118.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 13 December 2010, revised 3 March 2011 and accepted for publication 6 March 2011</unparsedEditorialHistory><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="0"></count></countGroup><titleGroup><title type="main">A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets in <i>Corynebacterium pseudotuberculosis</i> and other CMN Group of Human Pathogens</title><title type="shortAuthors"><b>Barh et al.</b></title><title type="short"><b>Novel Genomics Approach for Common Targets in <i>C. pseudotuberculosis</i> and CMN Group of Pathogens</b></title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1 #a2" corresponding="yes"><personName><givenNames>Debmalya</givenNames><familyName>Barh</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1 #a3"><personName><givenNames>Neha</givenNames><familyName>Jain</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1 #a3"><personName><givenNames>Sandeep</givenNames><familyName>Tiwari</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a1 #a2"><personName><givenNames>Bibhu Prasad</givenNames><familyName>Parida</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a4"><personName><givenNames>Vivian</givenNames><familyName>D’Afonseca</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a5"><personName><givenNames>Liwei</givenNames><familyName>Li</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a4"><personName><givenNames>Amjad</givenNames><familyName>Ali</familyName></personName></creator><creator creatorRole="author" xml:id="cr8" affiliationRef="#a4"><personName><givenNames>Anderson Rodrigues</givenNames><familyName>Santos</familyName></personName></creator><creator creatorRole="author" xml:id="cr9" affiliationRef="#a4"><personName><givenNames>Luís Carlos</givenNames><familyName>Guimarães</familyName></personName></creator><creator creatorRole="author" xml:id="cr10" affiliationRef="#a4"><personName><givenNames>Siomar</givenNames><familyName>de Castro Soares</familyName></personName></creator><creator creatorRole="author" xml:id="cr11" affiliationRef="#a4"><personName><givenNames>Anderson</givenNames><familyName>Miyoshi</familyName></personName></creator><creator creatorRole="author" xml:id="cr12" affiliationRef="#a6"><personName><givenNames>Atanu</givenNames><familyName>Bhattacharjee</familyName></personName></creator><creator creatorRole="author" xml:id="cr13" affiliationRef="#a2"><personName><givenNames>Amarendra Narayan</givenNames><familyName>Misra</familyName></personName></creator><creator creatorRole="author" xml:id="cr14" affiliationRef="#a7"><personName><givenNames>Artur</givenNames><familyName>Silva</familyName></personName></creator><creator creatorRole="author" xml:id="cr15" affiliationRef="#a3"><personName><givenNames>Anil</givenNames><familyName>Kumar</familyName></personName></creator><creator creatorRole="author" xml:id="cr16" affiliationRef="#a4"><personName><givenNames>Vasco</givenNames><familyName>Azevedo</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="IN"><unparsedAffiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="IN"><unparsedAffiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</unparsedAffiliation></affiliation><affiliation xml:id="a3" countryCode="IN"><unparsedAffiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</unparsedAffiliation></affiliation><affiliation xml:id="a4" countryCode="BR"><unparsedAffiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</unparsedAffiliation></affiliation><affiliation xml:id="a5" countryCode="US"><unparsedAffiliation>Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA</unparsedAffiliation></affiliation><affiliation xml:id="a6" countryCode="IN"><unparsedAffiliation>Department of Biotechnology and Bioinformatics, Bioinformatics Laboratory, North Eastern Hill University, Shillong, India</unparsedAffiliation></affiliation><affiliation xml:id="a7" countryCode="BR"><unparsedAffiliation>Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém‐PA, Brazil</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1"><i>Corynebacterium pseudotuberculosis</i></keyword><keyword xml:id="k2">drug and vaccine targets</keyword><keyword xml:id="k3">minimal genome</keyword><keyword xml:id="k4">subtractive genomics</keyword></keywordGroup><supportingInformation><p><b>Table S1.</b> Selected 38 common targets in CMN group of pathogens including <i>Cp</i>.</p><p><b>Table S2.</b> Comparative 3D modeling data.</p><p><b>Table S3.</b> Hits properties of top five compounds for each selected proteins.</p><p><b>Table S4.</b> Lists the protein residue IDs that are in contact with at least one of the top five compounds.</p><supportingInfoItem><mediaResource alt="supporting info item" href="urn-x:wiley:17470277:media:cbdd1118:CBDD_1118_sm_TableS1_V2"></mediaResource><caption>Supporting info item</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting info item" href="urn-x:wiley:17470277:media:cbdd1118:CBDD_1118_sm_TableS2"></mediaResource><caption>Supporting info item</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting info item" href="urn-x:wiley:17470277:media:cbdd1118:CBDD_1118_sm_TableS3"></mediaResource><caption>Supporting info item</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting info item" href="urn-x:wiley:17470277:media:cbdd1118:CBDD_1118_sm_TableS4"></mediaResource><caption>Supporting info item</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><p>Caseous lymphadenitis is a chronic goat and sheep disease caused by <i>Corynebacterium pseudotuberculosis</i> (<i>Cp</i>) that accounts for a huge economic loss worldwide. Proper vaccination or medication is not available because of the lack of understanding of molecular biology of the pathogen. In a recent approach, four <i>Cp</i> (CpFrc41, <i>Cp1002</i>, <i>CpC231</i>, and <i>CpI‐19</i>) genomes were sequenced to elucidate the molecular pathology of the bacteria. In this study, using these four genome sequences along with other eight genomes (total 12 genomes) and a novel subtractive genomics approach (first time ever applied to a veterinary pathogen), we identified potential conserved common drug and vaccine targets of these four <i>Cp</i> strains along with other <i>Corybacterium, Mycobacterium</i> and <i>Nocardia</i> (CMN) group of human pathogens (<i>Corynebacterium diphtheriae</i> and <i>Mycobacterium tuberculosis</i>) considering goat, sheep, bovine, horse, and human as the most affected hosts. The minimal genome of <i>Cp1002</i> was found to consist of 724 genes, and 20 conserved common targets (to all <i>Cp</i> strains as well as CMN group of pathogens) from various metabolic pathways (13 from host‐pathogen common and seven from pathogen’s unique pathways) are potential targets irrespective of all hosts considered. ubiA from host‐pathogen common pathway and an ABC‐like transporter from unique pathways may serve dual (drug and vaccine) targets. Two <i>Corynebacterium‐</i>specific (mscL and resB) and one broad‐spectrum (rpmB) novel targets were also identified. Strain‐specific targets are also discussed. Six important targets were subjected to virtual screening, and one compound was found to be potent enough to render two targets (cdc and nrdL). We are currently validating all identified targets and lead compounds.</p></abstract><abstract type="graphical"><p>Various metabolic pathway related common, conserved, novel, and dual targets (drug and vaccine) in <i>C. diphtheriae, M. tuberculosis,</i> and four <i>C. pseudotuberculosi</i>s strains are identified using total 12 genomes (4 are newly sequenced) and a novel subtractive genomic approach. Applying virtual screening, one compound is selected that can render two different targets cdc and nrdL simultaneously <blockFixed type="graphic" xml:id="f1ga"><mediaResourceGroup><mediaResource alt="image" href="urn:x-wiley:17470277:media:CBDD1118:CBDD_1118_f1ga"></mediaResource><mediaResource alt="image" mimeType="image/gif" rendition="webOriginal" href=""></mediaResource><mediaResource alt="image" mimeType="image/gif" rendition="webHiRes" href=""></mediaResource></mediaResourceGroup></blockFixed></p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets in Corynebacterium pseudotuberculosis and other CMN Group of Human Pathogens</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Novel Genomics Approach for Common Targets in C. pseudotuberculosis and CMN Group of Pathogens</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets in Corynebacterium pseudotuberculosis and other CMN Group of Human Pathogens</title></titleInfo><name type="personal"><namePart type="given">Debmalya</namePart><namePart type="family">Barh</namePart><affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</affiliation><affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</affiliation><description>Correspondence: </description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Neha</namePart><namePart type="family">Jain</namePart><affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</affiliation><affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sandeep</namePart><namePart type="family">Tiwari</namePart><affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</affiliation><affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bibhu Prasad</namePart><namePart type="family">Parida</namePart><affiliation>Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India</affiliation><affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vivian</namePart><namePart type="family">D’Afonseca</namePart><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Liwei</namePart><namePart type="family">Li</namePart><affiliation>Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Amjad</namePart><namePart type="family">Ali</namePart><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anderson Rodrigues</namePart><namePart type="family">Santos</namePart><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Luís Carlos</namePart><namePart type="family">Guimarães</namePart><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Siomar</namePart><namePart type="family">de Castro Soares</namePart><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anderson</namePart><namePart type="family">Miyoshi</namePart><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Atanu</namePart><namePart type="family">Bhattacharjee</namePart><affiliation>Department of Biotechnology and Bioinformatics, Bioinformatics Laboratory, North Eastern Hill University, Shillong, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Amarendra Narayan</namePart><namePart type="family">Misra</namePart><affiliation>Department of Biosciences and Biotechnology, School of Biotechnology, Fakir Mohan University, Jnan Bigyan Vihar, Balasore, Orissa, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Artur</namePart><namePart type="family">Silva</namePart><affiliation>Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém‐PA, Brazil</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anil</namePart><namePart type="family">Kumar</namePart><affiliation>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vasco</namePart><namePart type="family">Azevedo</namePart><affiliation>Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 486, CEP 31270‐901, Belo Horizonte, Minas Gerais, Brazil</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2011-07</dateIssued><edition>Received 13 December 2010, revised 3 March 2011 and accepted for publication 6 March 2011</edition><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">3</extent></physicalDescription><abstract lang="en">Caseous lymphadenitis is a chronic goat and sheep disease caused by Corynebacterium pseudotuberculosis (Cp) that accounts for a huge economic loss worldwide. Proper vaccination or medication is not available because of the lack of understanding of molecular biology of the pathogen. In a recent approach, four Cp (CpFrc41, Cp1002, CpC231, and CpI‐19) genomes were sequenced to elucidate the molecular pathology of the bacteria. In this study, using these four genome sequences along with other eight genomes (total 12 genomes) and a novel subtractive genomics approach (first time ever applied to a veterinary pathogen), we identified potential conserved common drug and vaccine targets of these four Cp strains along with other Corybacterium, Mycobacterium and Nocardia (CMN) group of human pathogens (Corynebacterium diphtheriae and Mycobacterium tuberculosis) considering goat, sheep, bovine, horse, and human as the most affected hosts. The minimal genome of Cp1002 was found to consist of 724 genes, and 20 conserved common targets (to all Cp strains as well as CMN group of pathogens) from various metabolic pathways (13 from host‐pathogen common and seven from pathogen’s unique pathways) are potential targets irrespective of all hosts considered. ubiA from host‐pathogen common pathway and an ABC‐like transporter from unique pathways may serve dual (drug and vaccine) targets. Two Corynebacterium‐specific (mscL and resB) and one broad‐spectrum (rpmB) novel targets were also identified. Strain‐specific targets are also discussed. Six important targets were subjected to virtual screening, and one compound was found to be potent enough to render two targets (cdc and nrdL). We are currently validating all identified targets and lead compounds.</abstract><abstract type="graphical">Various metabolic pathway related common, conserved, novel, and dual targets (drug and vaccine) in C. diphtheriae, M. tuberculosis, and four C. pseudotuberculosis strains are identified using total 12 genomes (4 are newly sequenced) and a novel subtractive genomic approach. Applying virtual screening, one compound is selected that can render two different targets cdc and nrdL simultaneously</abstract><subject lang="en"><genre>keywords</genre><topic>Corynebacterium pseudotuberculosis</topic><topic>drug and vaccine targets</topic><topic>minimal genome</topic><topic>subtractive genomics</topic></subject><relatedItem type="host"><titleInfo><title>Chemical Biology & Drug Design</title></titleInfo><genre type="journal">journal</genre><note type="content"> Table S1. Selected 38 common targets in CMN group of pathogens including Cp. Table S2. Comparative 3D modeling data. Table S3. Hits properties of top five compounds for each selected proteins. Table S4. Lists the protein residue IDs that are in contact with at least one of the top five compounds. Table S1. Selected 38 common targets in CMN group of pathogens including Cp. Table S2. Comparative 3D modeling data. Table S3. Hits properties of top five compounds for each selected proteins. Table S4. Lists the protein residue IDs that are in contact with at least one of the top five compounds. Table S1. Selected 38 common targets in CMN group of pathogens including Cp. Table S2. Comparative 3D modeling data. Table S3. Hits properties of top five compounds for each selected proteins. Table S4. Lists the protein residue IDs that are in contact with at least one of the top five compounds. Table S1. Selected 38 common targets in CMN group of pathogens including Cp. Table S2. Comparative 3D modeling data. Table S3. Hits properties of top five compounds for each selected proteins. Table S4. Lists the protein residue IDs that are in contact with at least one of the top five compounds.Supporting Info Item: Supporting info item - Supporting info item - Supporting info item - Supporting info item - </note><subject><genre>article-category</genre><topic>Research Article</topic></subject><identifier type="ISSN">1747-0277</identifier><identifier type="eISSN">1747-0285</identifier><identifier type="DOI">10.1111/(ISSN)1747-0285</identifier><identifier type="PublisherID">CBDD</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>78</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>73</start><end>84</end><total>13</total></extent></part></relatedItem><identifier type="istex">E90778391939DFC6D4731CC1D10B195633EDFA80</identifier><identifier type="DOI">10.1111/j.1747-0285.2011.01118.x</identifier><identifier type="ArticleID">CBDD1118</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2011 John Wiley & Sons A/S</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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