Tetanus toxin production is triggered by the transition from amino acid consumption to peptides.
Identifieur interne : 001676 ( Main/Corpus ); précédent : 001675; suivant : 001677Tetanus toxin production is triggered by the transition from amino acid consumption to peptides.
Auteurs : Cuauhtemoc Licona-Cassani ; Jennifer A. Steen ; Nicolas E. Zaragoza ; Glenn Moonen ; George Moutafis ; Mark P. Hodson ; John Power ; Lars K. Nielsen ; Esteban MarcellinSource :
- Anaerobe [ 1095-8274 ] ; 2016.
English descriptors
- KwdEn :
- Adaptation, Physiological (MeSH), Adenosine Triphosphate (metabolism), Amino Acid Sequence (MeSH), Amino Acids (chemistry), Amino Acids (physiology), Clostridium tetani (growth & development), Clostridium tetani (metabolism), Culture Media (chemistry), Energy Metabolism (MeSH), Fermentation (MeSH), Iron (metabolism), Oligopeptides (chemistry), Oligopeptides (physiology), Plasmids (genetics), Tetanus Toxin (biosynthesis), Tetanus Toxin (genetics), Transcriptome (MeSH), Virulence Factors (genetics).
- MESH :
- chemical , biosynthesis : Tetanus Toxin.
- chemical , chemistry : Amino Acids, Culture Media, Oligopeptides.
- chemical , genetics : Tetanus Toxin, Virulence Factors.
- chemical , metabolism : Adenosine Triphosphate, Iron.
- chemical , physiology : Amino Acids, Oligopeptides.
- genetics : Plasmids.
- growth & development : Clostridium tetani.
- metabolism : Clostridium tetani.
- Adaptation, Physiological, Amino Acid Sequence, Energy Metabolism, Fermentation, Transcriptome.
Abstract
Bacteria produce some of the most potent biomolecules known, of which many cause serious diseases such as tetanus. For prevention, billions of people and countless animals are immunised with the highly effective vaccine, industrially produced by large-scale fermentation. However, toxin production is often hampered by low yields and batch-to-batch variability. Improved productivity has been constrained by a lack of understanding of the molecular mechanisms controlling toxin production. Here we have developed a reproducible experimental framework for screening phenotypic determinants in Clostridium tetani under a process that mimics an industrial setting. We show that amino acid depletion induces production of the tetanus toxin. Using time-course transcriptomics and extracellular metabolomics to generate a 'fermentation atlas' that ascribe growth behaviour, nutrient consumption and gene expression to the fermentation phases, we found a subset of preferred amino acids. Exponential growth is characterised by the consumption of those amino acids followed by a slower exponential growth phase where peptides are consumed, and toxin is produced. The results aim at assisting in fermentation medium design towards the improvement of vaccine production yields and reproducibility. In conclusion, our work not only provides deep fermentation dynamics but represents the foundation for bioprocess design based on C. tetani physiological behaviour under industrial settings.
DOI: 10.1016/j.anaerobe.2016.07.006
PubMed: 27492724
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pubmed:27492724Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Tetanus toxin production is triggered by the transition from amino acid consumption to peptides.</title><author><name sortKey="Licona Cassani, Cuauhtemoc" sort="Licona Cassani, Cuauhtemoc" uniqKey="Licona Cassani C" first="Cuauhtemoc" last="Licona-Cassani">Cuauhtemoc Licona-Cassani</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia; National Laboratory of Genomics for Biodiversity (LANGEBIO), Cinvestav-IPN, Irapuato, Mexico.</nlm:affiliation></affiliation></author><author><name sortKey="Steen, Jennifer A" sort="Steen, Jennifer A" uniqKey="Steen J" first="Jennifer A" last="Steen">Jennifer A. Steen</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Zaragoza, Nicolas E" sort="Zaragoza, Nicolas E" uniqKey="Zaragoza N" first="Nicolas E" last="Zaragoza">Nicolas E. Zaragoza</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Moonen, Glenn" sort="Moonen, Glenn" uniqKey="Moonen G" first="Glenn" last="Moonen">Glenn Moonen</name><affiliation><nlm:affiliation>Zoetis, 45 Poplar Road, Parkville, VIC 3052, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Moutafis, George" sort="Moutafis, George" uniqKey="Moutafis G" first="George" last="Moutafis">George Moutafis</name><affiliation><nlm:affiliation>Zoetis, 45 Poplar Road, Parkville, VIC 3052, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Hodson, Mark P" sort="Hodson, Mark P" uniqKey="Hodson M" first="Mark P" last="Hodson">Mark P. Hodson</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia; Metabolomics Australia Queensland Node, AIBN, The University of Queensland, Brisbane, QLD 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Power, John" sort="Power, John" uniqKey="Power J" first="John" last="Power">John Power</name><affiliation><nlm:affiliation>Zoetis, 45 Poplar Road, Parkville, VIC 3052, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Nielsen, Lars K" sort="Nielsen, Lars K" uniqKey="Nielsen L" first="Lars K" last="Nielsen">Lars K. Nielsen</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Marcellin, Esteban" sort="Marcellin, Esteban" uniqKey="Marcellin E" first="Esteban" last="Marcellin">Esteban Marcellin</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: e.marcellin@uq.edu.au.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27492724</idno><idno type="pmid">27492724</idno><idno type="doi">10.1016/j.anaerobe.2016.07.006</idno><idno type="wicri:Area/Main/Corpus">001676</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001676</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Tetanus toxin production is triggered by the transition from amino acid consumption to peptides.</title><author><name sortKey="Licona Cassani, Cuauhtemoc" sort="Licona Cassani, Cuauhtemoc" uniqKey="Licona Cassani C" first="Cuauhtemoc" last="Licona-Cassani">Cuauhtemoc Licona-Cassani</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia; National Laboratory of Genomics for Biodiversity (LANGEBIO), Cinvestav-IPN, Irapuato, Mexico.</nlm:affiliation></affiliation></author><author><name sortKey="Steen, Jennifer A" sort="Steen, Jennifer A" uniqKey="Steen J" first="Jennifer A" last="Steen">Jennifer A. Steen</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Zaragoza, Nicolas E" sort="Zaragoza, Nicolas E" uniqKey="Zaragoza N" first="Nicolas E" last="Zaragoza">Nicolas E. Zaragoza</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Moonen, Glenn" sort="Moonen, Glenn" uniqKey="Moonen G" first="Glenn" last="Moonen">Glenn Moonen</name><affiliation><nlm:affiliation>Zoetis, 45 Poplar Road, Parkville, VIC 3052, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Moutafis, George" sort="Moutafis, George" uniqKey="Moutafis G" first="George" last="Moutafis">George Moutafis</name><affiliation><nlm:affiliation>Zoetis, 45 Poplar Road, Parkville, VIC 3052, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Hodson, Mark P" sort="Hodson, Mark P" uniqKey="Hodson M" first="Mark P" last="Hodson">Mark P. Hodson</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia; Metabolomics Australia Queensland Node, AIBN, The University of Queensland, Brisbane, QLD 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Power, John" sort="Power, John" uniqKey="Power J" first="John" last="Power">John Power</name><affiliation><nlm:affiliation>Zoetis, 45 Poplar Road, Parkville, VIC 3052, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Nielsen, Lars K" sort="Nielsen, Lars K" uniqKey="Nielsen L" first="Lars K" last="Nielsen">Lars K. Nielsen</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Marcellin, Esteban" sort="Marcellin, Esteban" uniqKey="Marcellin E" first="Esteban" last="Marcellin">Esteban Marcellin</name><affiliation><nlm:affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: e.marcellin@uq.edu.au.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Anaerobe</title><idno type="eISSN">1095-8274</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptation, Physiological (MeSH)</term><term>Adenosine Triphosphate (metabolism)</term><term>Amino Acid Sequence (MeSH)</term><term>Amino Acids (chemistry)</term><term>Amino Acids (physiology)</term><term>Clostridium tetani (growth & development)</term><term>Clostridium tetani (metabolism)</term><term>Culture Media (chemistry)</term><term>Energy Metabolism (MeSH)</term><term>Fermentation (MeSH)</term><term>Iron (metabolism)</term><term>Oligopeptides (chemistry)</term><term>Oligopeptides (physiology)</term><term>Plasmids (genetics)</term><term>Tetanus Toxin (biosynthesis)</term><term>Tetanus Toxin (genetics)</term><term>Transcriptome (MeSH)</term><term>Virulence Factors (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Tetanus Toxin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Amino Acids</term><term>Culture Media</term><term>Oligopeptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Tetanus Toxin</term><term>Virulence Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine Triphosphate</term><term>Iron</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Amino Acids</term><term>Oligopeptides</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Plasmids</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Clostridium tetani</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Clostridium tetani</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adaptation, Physiological</term><term>Amino Acid Sequence</term><term>Energy Metabolism</term><term>Fermentation</term><term>Transcriptome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Bacteria produce some of the most potent biomolecules known, of which many cause serious diseases such as tetanus. For prevention, billions of people and countless animals are immunised with the highly effective vaccine, industrially produced by large-scale fermentation. However, toxin production is often hampered by low yields and batch-to-batch variability. Improved productivity has been constrained by a lack of understanding of the molecular mechanisms controlling toxin production. Here we have developed a reproducible experimental framework for screening phenotypic determinants in Clostridium tetani under a process that mimics an industrial setting. We show that amino acid depletion induces production of the tetanus toxin. Using time-course transcriptomics and extracellular metabolomics to generate a 'fermentation atlas' that ascribe growth behaviour, nutrient consumption and gene expression to the fermentation phases, we found a subset of preferred amino acids. Exponential growth is characterised by the consumption of those amino acids followed by a slower exponential growth phase where peptides are consumed, and toxin is produced. The results aim at assisting in fermentation medium design towards the improvement of vaccine production yields and reproducibility. In conclusion, our work not only provides deep fermentation dynamics but represents the foundation for bioprocess design based on C. tetani physiological behaviour under industrial settings.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27492724</PMID><DateCompleted><Year>2017</Year><Month>01</Month><Day>19</Day></DateCompleted><DateRevised><Year>2017</Year><Month>01</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1095-8274</ISSN><JournalIssue CitedMedium="Internet"><Volume>41</Volume><PubDate><Year>2016</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Anaerobe</Title><ISOAbbreviation>Anaerobe</ISOAbbreviation></Journal><ArticleTitle>Tetanus toxin production is triggered by the transition from amino acid consumption to peptides.</ArticleTitle><Pagination><MedlinePgn>113-124</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1075-9964(16)30090-7</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.anaerobe.2016.07.006</ELocationID><Abstract><AbstractText>Bacteria produce some of the most potent biomolecules known, of which many cause serious diseases such as tetanus. For prevention, billions of people and countless animals are immunised with the highly effective vaccine, industrially produced by large-scale fermentation. However, toxin production is often hampered by low yields and batch-to-batch variability. Improved productivity has been constrained by a lack of understanding of the molecular mechanisms controlling toxin production. Here we have developed a reproducible experimental framework for screening phenotypic determinants in Clostridium tetani under a process that mimics an industrial setting. We show that amino acid depletion induces production of the tetanus toxin. Using time-course transcriptomics and extracellular metabolomics to generate a 'fermentation atlas' that ascribe growth behaviour, nutrient consumption and gene expression to the fermentation phases, we found a subset of preferred amino acids. Exponential growth is characterised by the consumption of those amino acids followed by a slower exponential growth phase where peptides are consumed, and toxin is produced. The results aim at assisting in fermentation medium design towards the improvement of vaccine production yields and reproducibility. In conclusion, our work not only provides deep fermentation dynamics but represents the foundation for bioprocess design based on C. tetani physiological behaviour under industrial settings.</AbstractText><CopyrightInformation>Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Licona-Cassani</LastName><ForeName>Cuauhtemoc</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia; National Laboratory of Genomics for Biodiversity (LANGEBIO), Cinvestav-IPN, Irapuato, Mexico.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Steen</LastName><ForeName>Jennifer A</ForeName><Initials>JA</Initials><AffiliationInfo><Affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zaragoza</LastName><ForeName>Nicolas E</ForeName><Initials>NE</Initials><AffiliationInfo><Affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moonen</LastName><ForeName>Glenn</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Zoetis, 45 Poplar Road, Parkville, VIC 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moutafis</LastName><ForeName>George</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Zoetis, 45 Poplar Road, Parkville, VIC 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hodson</LastName><ForeName>Mark P</ForeName><Initials>MP</Initials><AffiliationInfo><Affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia; Metabolomics Australia Queensland Node, AIBN, The University of Queensland, Brisbane, QLD 4072, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Power</LastName><ForeName>John</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Zoetis, 45 Poplar Road, Parkville, VIC 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nielsen</LastName><ForeName>Lars K</ForeName><Initials>LK</Initials><AffiliationInfo><Affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marcellin</LastName><ForeName>Esteban</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: e.marcellin@uq.edu.au.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>08</Month><Day>01</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Anaerobe</MedlineTA><NlmUniqueID>9505216</NlmUniqueID><ISSNLinking>1075-9964</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000596">Amino Acids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D003470">Culture Media</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009842">Oligopeptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013744">Tetanus Toxin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D037521">Virulence Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>8L70Q75FXE</RegistryNumber><NameOfSubstance UI="D000255">Adenosine Triphosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>E1UOL152H7</RegistryNumber><NameOfSubstance UI="D007501">Iron</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000222" MajorTopicYN="N">Adaptation, Physiological</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000255" MajorTopicYN="N">Adenosine Triphosphate</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000596" MajorTopicYN="N">Amino Acids</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003017" MajorTopicYN="N">Clostridium tetani</DescriptorName><QualifierName UI="Q000254" MajorTopicYN="N">growth & development</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003470" MajorTopicYN="N">Culture Media</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004734" MajorTopicYN="N">Energy Metabolism</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005285" MajorTopicYN="N">Fermentation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007501" MajorTopicYN="N">Iron</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009842" MajorTopicYN="N">Oligopeptides</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010957" MajorTopicYN="N">Plasmids</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013744" MajorTopicYN="N">Tetanus Toxin</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059467" MajorTopicYN="N">Transcriptome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D037521" MajorTopicYN="N">Virulence Factors</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Clostridium tetani</Keyword><Keyword MajorTopicYN="N">Fermentation maps</Keyword><Keyword MajorTopicYN="N">Systems biology</Keyword><Keyword MajorTopicYN="N">TeTN production</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>04</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2016</Year><Month>07</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>07</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>8</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>1</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>8</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27492724</ArticleId><ArticleId IdType="pii">S1075-9964(16)30090-7</ArticleId><ArticleId IdType="doi">10.1016/j.anaerobe.2016.07.006</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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