Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii.
Identifieur interne : 001618 ( Ncbi/Merge ); précédent : 001617; suivant : 001619Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii.
Auteurs : Carl Song [Canada] ; Melissa A. Chiasson ; Nirvana Nursimulu ; Stacy S. Hung ; James Wasmuth ; Michael E. Grigg ; John ParkinsonSource :
- Molecular systems biology [ 1744-4292 ] ; 2013.
English descriptors
- KwdEn :
- Antiprotozoal Agents (pharmacology), Diphosphonates (pharmacology), Drug Resistance (drug effects), Fibroblasts (cytology), Fibroblasts (parasitology), Gene Expression Regulation, Host Specificity, Host-Parasite Interactions, Humans, Metabolic Engineering, Metabolic Networks and Pathways, Models, Genetic, Quinolines (pharmacology), Species Specificity, Toxoplasma (drug effects), Toxoplasma (genetics), Toxoplasma (metabolism), Toxoplasma (pathogenicity), Virulence.
- MESH :
- chemical , pharmacology : Antiprotozoal Agents, Diphosphonates, Quinolines.
- cytology : Fibroblasts.
- drug effects : Drug Resistance, Toxoplasma.
- genetics : Toxoplasma.
- metabolism : Toxoplasma.
- parasitology : Fibroblasts.
- pathogenicity : Toxoplasma.
- Gene Expression Regulation, Host Specificity, Host-Parasite Interactions, Humans, Metabolic Engineering, Metabolic Networks and Pathways, Models, Genetic, Species Specificity, Virulence.
Abstract
Increasingly, metabolic potential is proving to be a critical determinant governing a pathogen's virulence as well as its capacity to expand its host range. To understand the potential contribution of metabolism to strain-specific infectivity differences, we present a constraint-based metabolic model of the opportunistic parasite, Toxoplasma gondii. Dominated by three clonal strains (Type I, II, and III demonstrating distinct virulence profiles), T. gondii exhibits a remarkably broad host range. Integrating functional genomic data, our model (which we term as iCS382) reveals that observed strain-specific differences in growth rates are driven by altered capacities for energy production. We further predict strain-specific differences in drug susceptibilities and validate one of these predictions in a drug-based assay, with a Type I strain demonstrating resistance to inhibitors that are effective against a Type II strain. We propose that these observed differences reflect an evolutionary strategy that allows the parasite to extend its host range, as well as result in a subsequent partitioning into discrete strains that display altered virulence profiles across different hosts, different organs, and even cell types.
DOI: 10.1038/msb.2013.62
PubMed: 24247825
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000838
- to stream PubMed, to step Curation: 000838
- to stream PubMed, to step Checkpoint: 000838
Links to Exploration step
pubmed:24247825Le document en format XML
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Chiasson</name></author><author><name sortKey="Nursimulu, Nirvana" sort="Nursimulu, Nirvana" uniqKey="Nursimulu N" first="Nirvana" last="Nursimulu">Nirvana Nursimulu</name></author><author><name sortKey="Hung, Stacy S" sort="Hung, Stacy S" uniqKey="Hung S" first="Stacy S" last="Hung">Stacy S. Hung</name></author><author><name sortKey="Wasmuth, James" sort="Wasmuth, James" uniqKey="Wasmuth J" first="James" last="Wasmuth">James Wasmuth</name></author><author><name sortKey="Grigg, Michael E" sort="Grigg, Michael E" uniqKey="Grigg M" first="Michael E" last="Grigg">Michael E. 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Chiasson</name></author><author><name sortKey="Nursimulu, Nirvana" sort="Nursimulu, Nirvana" uniqKey="Nursimulu N" first="Nirvana" last="Nursimulu">Nirvana Nursimulu</name></author><author><name sortKey="Hung, Stacy S" sort="Hung, Stacy S" uniqKey="Hung S" first="Stacy S" last="Hung">Stacy S. Hung</name></author><author><name sortKey="Wasmuth, James" sort="Wasmuth, James" uniqKey="Wasmuth J" first="James" last="Wasmuth">James Wasmuth</name></author><author><name sortKey="Grigg, Michael E" sort="Grigg, Michael E" uniqKey="Grigg M" first="Michael E" last="Grigg">Michael E. Grigg</name></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name></author></analytic><series><title level="j">Molecular systems biology</title><idno type="eISSN">1744-4292</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiprotozoal Agents (pharmacology)</term><term>Diphosphonates (pharmacology)</term><term>Drug Resistance (drug effects)</term><term>Fibroblasts (cytology)</term><term>Fibroblasts (parasitology)</term><term>Gene Expression Regulation</term><term>Host Specificity</term><term>Host-Parasite Interactions</term><term>Humans</term><term>Metabolic Engineering</term><term>Metabolic Networks and Pathways</term><term>Models, Genetic</term><term>Quinolines (pharmacology)</term><term>Species Specificity</term><term>Toxoplasma (drug effects)</term><term>Toxoplasma (genetics)</term><term>Toxoplasma (metabolism)</term><term>Toxoplasma (pathogenicity)</term><term>Virulence</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiprotozoal Agents</term><term>Diphosphonates</term><term>Quinolines</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Fibroblasts</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Drug Resistance</term><term>Toxoplasma</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Toxoplasma</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Toxoplasma</term></keywords><keywords scheme="MESH" qualifier="parasitology" xml:lang="en"><term>Fibroblasts</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Toxoplasma</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Gene Expression Regulation</term><term>Host Specificity</term><term>Host-Parasite Interactions</term><term>Humans</term><term>Metabolic Engineering</term><term>Metabolic Networks and Pathways</term><term>Models, Genetic</term><term>Species Specificity</term><term>Virulence</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Increasingly, metabolic potential is proving to be a critical determinant governing a pathogen's virulence as well as its capacity to expand its host range. To understand the potential contribution of metabolism to strain-specific infectivity differences, we present a constraint-based metabolic model of the opportunistic parasite, Toxoplasma gondii. Dominated by three clonal strains (Type I, II, and III demonstrating distinct virulence profiles), T. gondii exhibits a remarkably broad host range. Integrating functional genomic data, our model (which we term as iCS382) reveals that observed strain-specific differences in growth rates are driven by altered capacities for energy production. We further predict strain-specific differences in drug susceptibilities and validate one of these predictions in a drug-based assay, with a Type I strain demonstrating resistance to inhibitors that are effective against a Type II strain. We propose that these observed differences reflect an evolutionary strategy that allows the parasite to extend its host range, as well as result in a subsequent partitioning into discrete strains that display altered virulence profiles across different hosts, different organs, and even cell types.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24247825</PMID><DateCreated><Year>2013</Year><Month>11</Month><Day>19</Day></DateCreated><DateCompleted><Year>2014</Year><Month>03</Month><Day>03</Day></DateCompleted><DateRevised><Year>2016</Year><Month>10</Month><Day>19</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1744-4292</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><PubDate><Year>2013</Year><Month>Nov</Month><Day>19</Day></PubDate></JournalIssue><Title>Molecular systems biology</Title><ISOAbbreviation>Mol. Syst. Biol.</ISOAbbreviation></Journal><ArticleTitle>Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii.</ArticleTitle><Pagination><MedlinePgn>708</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/msb.2013.62</ELocationID><Abstract><AbstractText>Increasingly, metabolic potential is proving to be a critical determinant governing a pathogen's virulence as well as its capacity to expand its host range. To understand the potential contribution of metabolism to strain-specific infectivity differences, we present a constraint-based metabolic model of the opportunistic parasite, Toxoplasma gondii. Dominated by three clonal strains (Type I, II, and III demonstrating distinct virulence profiles), T. gondii exhibits a remarkably broad host range. Integrating functional genomic data, our model (which we term as iCS382) reveals that observed strain-specific differences in growth rates are driven by altered capacities for energy production. We further predict strain-specific differences in drug susceptibilities and validate one of these predictions in a drug-based assay, with a Type I strain demonstrating resistance to inhibitors that are effective against a Type II strain. We propose that these observed differences reflect an evolutionary strategy that allows the parasite to extend its host range, as well as result in a subsequent partitioning into discrete strains that display altered virulence profiles across different hosts, different organs, and even cell types.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Carl</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>1] Program in Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chiasson</LastName><ForeName>Melissa A</ForeName><Initials>MA</Initials></Author><Author ValidYN="Y"><LastName>Nursimulu</LastName><ForeName>Nirvana</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Hung</LastName><ForeName>Stacy S</ForeName><Initials>SS</Initials></Author><Author ValidYN="Y"><LastName>Wasmuth</LastName><ForeName>James</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Grigg</LastName><ForeName>Michael E</ForeName><Initials>ME</Initials></Author><Author ValidYN="Y"><LastName>Parkinson</LastName><ForeName>John</ForeName><Initials>J</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MOP #84556</GrantID><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant><Grant><Agency>Intramural NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>11</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Mol Syst Biol</MedlineTA><NlmUniqueID>101235389</NlmUniqueID><ISSNLinking>1744-4292</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000981">Antiprotozoal Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004164">Diphosphonates</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011804">Quinolines</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>J Infect Dis. 2002 Jun 1;185(11):1637-43</RefSource><PMID Version="1">12023770</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Curr Opin Microbiol. 2002 Aug;5(4):438-42</RefSource><PMID 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Version="1">11846609</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mol Microbiol. 2002 Mar;43(5):1309-18</RefSource><PMID Version="1">11918815</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000981" MajorTopicYN="N">Antiprotozoal Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004164" MajorTopicYN="N">Diphosphonates</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004351" MajorTopicYN="N">Drug Resistance</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005347" MajorTopicYN="N">Fibroblasts</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000469" MajorTopicYN="Y">parasitology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005786" MajorTopicYN="Y">Gene Expression Regulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058507" MajorTopicYN="N">Host Specificity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006790" MajorTopicYN="N">Host-Parasite Interactions</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D060847" MajorTopicYN="N">Metabolic Engineering</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053858" MajorTopicYN="Y">Metabolic Networks and Pathways</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008957" MajorTopicYN="N">Models, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011804" MajorTopicYN="N">Quinolines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013045" MajorTopicYN="N">Species Specificity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014122" MajorTopicYN="N">Toxoplasma</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000472" MajorTopicYN="Y">pathogenicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014774" MajorTopicYN="N">Virulence</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4039375</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2013</Year><Month>05</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2013</Year><Month>10</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>11</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>11</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>3</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">24247825</ArticleId><ArticleId IdType="pii">msb201362</ArticleId><ArticleId IdType="doi">10.1038/msb.2013.62</ArticleId><ArticleId IdType="pmc">PMC4039375</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><noCountry><name sortKey="Chiasson, Melissa A" sort="Chiasson, Melissa A" uniqKey="Chiasson M" first="Melissa A" last="Chiasson">Melissa A. Chiasson</name><name sortKey="Grigg, Michael E" sort="Grigg, Michael E" uniqKey="Grigg M" first="Michael E" last="Grigg">Michael E. Grigg</name><name sortKey="Hung, Stacy S" sort="Hung, Stacy S" uniqKey="Hung S" first="Stacy S" last="Hung">Stacy S. Hung</name><name sortKey="Nursimulu, Nirvana" sort="Nursimulu, Nirvana" uniqKey="Nursimulu N" first="Nirvana" last="Nursimulu">Nirvana Nursimulu</name><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><name sortKey="Wasmuth, James" sort="Wasmuth, James" uniqKey="Wasmuth J" first="James" last="Wasmuth">James Wasmuth</name></noCountry><country name="Canada"><region name="Ontario"><name sortKey="Song, Carl" sort="Song, Carl" uniqKey="Song C" first="Carl" last="Song">Carl Song</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|wiki= Wicri/Canada
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|clé= pubmed:24247825
|texte= Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii.
}}
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| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
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