A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets in Corynebacterium pseudotuberculosis and other CMN Group of Human Pathogens
Identifieur interne : 000536 ( Main/Exploration ); précédent : 000535; suivant : 000537A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets in Corynebacterium pseudotuberculosis and other CMN Group of Human Pathogens
Auteurs : Debmalya Barh [Inde] ; Neha Jain [Inde] ; Sandeep Tiwari [Inde] ; Bibhu Prasad Parida [Inde] ; Vivian D Fonseca [Brésil] ; Liwei Li [États-Unis] ; Amjad Ali [Brésil] ; Anderson Rodrigues Santos [Brésil] ; Luís Carlos Guimarães [Brésil] ; Siomar De Castro Soares [Brésil] ; Anderson Miyoshi [Brésil] ; Atanu Bhattacharjee [Inde] ; Amarendra Narayan Misra [Inde] ; Artur Silva [Brésil] ; Anil Kumar [Inde] ; Vasco Azevedo [Brésil]Source :
- Chemical Biology & Drug Design [ 1747-0277 ] ; 2011-07.
English descriptors
- KwdEn :
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.
Url:
DOI: 10.1111/j.1747-0285.2011.01118.x
Affiliations:
- Brésil, Inde, États-Unis
- Indiana, Minas Gerais, Pará
- Belo Horizonte
- Université fédérale du Minas Gerais
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Orissa</wicri:regionArea><wicri:noRegion>Orissa</wicri:noRegion></affiliation></author><author><name sortKey="Silva, Artur" sort="Silva, Artur" uniqKey="Silva A" first="Artur" last="Silva">Artur Silva</name><affiliation wicri:level="2"><country xml:lang="fr">Brésil</country><wicri:regionArea>Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém‐PA</wicri:regionArea><placeName><region type="state">Pará</region></placeName></affiliation></author><author><name sortKey="Kumar, Anil" sort="Kumar, Anil" uniqKey="Kumar A" first="Anil" last="Kumar">Anil Kumar</name><affiliation wicri:level="1"><country xml:lang="fr">Inde</country><wicri:regionArea>School of Biotechnology, Devi Ahilya University, Khandwa Rd., Indore</wicri:regionArea><wicri:noRegion>Indore</wicri:noRegion></affiliation></author><author><name sortKey="Azevedo, Vasco" sort="Azevedo, Vasco" uniqKey="Azevedo V" first="Vasco" last="Azevedo">Vasco Azevedo</name><affiliation wicri:level="4"><country xml:lang="fr">Brésil</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Minas Gerais</region><settlement type="city">Belo Horizonte</settlement></placeName><orgName type="university">Université fédérale du Minas Gerais</orgName></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><affiliations><list><country><li>Brésil</li><li>Inde</li><li>États-Unis</li></country><region><li>Indiana</li><li>Minas Gerais</li><li>Pará</li></region><settlement><li>Belo Horizonte</li></settlement><orgName><li>Université fédérale du Minas Gerais</li></orgName></list><tree><country name="Inde"><noRegion><name sortKey="Barh, Debmalya" sort="Barh, Debmalya" uniqKey="Barh D" first="Debmalya" last="Barh">Debmalya Barh</name></noRegion><name sortKey="Barh, Debmalya" sort="Barh, Debmalya" uniqKey="Barh D" first="Debmalya" last="Barh">Debmalya Barh</name><name sortKey="Bhattacharjee, Atanu" sort="Bhattacharjee, Atanu" uniqKey="Bhattacharjee A" first="Atanu" last="Bhattacharjee">Atanu Bhattacharjee</name><name sortKey="Jain, Neha" sort="Jain, Neha" uniqKey="Jain N" first="Neha" last="Jain">Neha Jain</name><name sortKey="Jain, Neha" sort="Jain, Neha" uniqKey="Jain N" first="Neha" last="Jain">Neha Jain</name><name sortKey="Kumar, Anil" sort="Kumar, Anil" uniqKey="Kumar A" first="Anil" last="Kumar">Anil Kumar</name><name sortKey="Misra, Amarendra Narayan" sort="Misra, Amarendra Narayan" uniqKey="Misra A" first="Amarendra Narayan" last="Misra">Amarendra Narayan Misra</name><name sortKey="Parida, Bibhu Prasad" sort="Parida, Bibhu Prasad" uniqKey="Parida B" first="Bibhu Prasad" last="Parida">Bibhu Prasad Parida</name><name sortKey="Parida, Bibhu Prasad" sort="Parida, Bibhu Prasad" uniqKey="Parida B" first="Bibhu Prasad" last="Parida">Bibhu Prasad Parida</name><name sortKey="Tiwari, Sandeep" sort="Tiwari, Sandeep" uniqKey="Tiwari S" first="Sandeep" last="Tiwari">Sandeep Tiwari</name><name sortKey="Tiwari, Sandeep" sort="Tiwari, Sandeep" uniqKey="Tiwari S" first="Sandeep" last="Tiwari">Sandeep Tiwari</name></country><country name="Brésil"><region name="Minas Gerais"><name sortKey="D Fonseca, Vivian" sort="D Fonseca, Vivian" uniqKey="D Fonseca V" first="Vivian" last="D Fonseca">Vivian D Fonseca</name></region><name sortKey="Ali, Amjad" sort="Ali, Amjad" uniqKey="Ali A" first="Amjad" last="Ali">Amjad Ali</name><name sortKey="Azevedo, Vasco" sort="Azevedo, Vasco" uniqKey="Azevedo V" first="Vasco" last="Azevedo">Vasco Azevedo</name><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><name sortKey="Guimaraes, Luis Carlos" sort="Guimaraes, Luis Carlos" uniqKey="Guimaraes L" first="Luís Carlos" last="Guimarães">Luís Carlos Guimarães</name><name sortKey="Miyoshi, Anderson" sort="Miyoshi, Anderson" uniqKey="Miyoshi A" first="Anderson" last="Miyoshi">Anderson Miyoshi</name><name sortKey="Santos, Anderson Rodrigues" sort="Santos, Anderson Rodrigues" uniqKey="Santos A" first="Anderson Rodrigues" last="Santos">Anderson Rodrigues Santos</name><name sortKey="Silva, Artur" sort="Silva, Artur" uniqKey="Silva A" first="Artur" last="Silva">Artur Silva</name></country><country name="États-Unis"><region name="Indiana"><name sortKey="Li, Liwei" sort="Li, Liwei" uniqKey="Li L" first="Liwei" last="Li">Liwei Li</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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