A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains.
Identifieur interne : 002409 ( PubMed/Checkpoint ); précédent : 002408; suivant : 002410A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains.
Auteurs : Srikanth Mairpady Shambat [Suède] ; Nikolai Siemens [Suède] ; Ian R. Monk [Australie] ; Disha B. Mohan [Inde] ; Santhosh Mukundan [États-Unis] ; Karthickeyan Chella Krishnan [États-Unis] ; Sushma Prabhakara [Inde] ; Johanna Sn Ll [Suède] ; Angela Kearns [Royaume-Uni] ; Francois Vandenesch ; Mattias Svensson [Suède] ; Malak Kotb [États-Unis] ; Balasubramanian Gopal [Inde] ; Gayathri Arakere [Inde] ; Anna Norrby-Teglund [Suède]Source :
- Scientific reports [ 2045-2322 ] ; 2016.
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections. One of the highly successful and rapidly disseminating clones is MRSA ST22 commonly associated with skin tropism. Here we show that a naturally occurring single amino acid substitution (tyrosine to cysteine) at position 223 of AgrC determines starkly different ST22 S. aureus virulence phenotypes, e.g. cytotoxic or colonizing, as evident in both in vitro and in vivo skin infections. Y223C amino acid substitution destabilizes AgrC-AgrA interaction leading to a colonizing phenotype characterized by upregulation of bacterial surface proteins. The colonizing phenotype strains cause less severe skin tissue damage, show decreased susceptibility towards the antimicrobial LL-37 and induce autophagy. In contrast, cytotoxic strains with tyrosine at position 223 of AgrC cause infections characterized by inflammasome activation and severe skin tissue pathology. Taken together, the study demonstrates how a single amino acid substitution in the histidine kinase receptor AgrC of ST22 strains determines virulence properties and infection outcome.
DOI: 10.1038/srep31360
PubMed: 27511873
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains.</title><author><name sortKey="Mairpady Shambat, Srikanth" sort="Mairpady Shambat, Srikanth" uniqKey="Mairpady Shambat S" first="Srikanth" last="Mairpady Shambat">Srikanth Mairpady Shambat</name><affiliation wicri:level="1"><nlm:affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86</wicri:regionArea><wicri:noRegion>141 86</wicri:noRegion></affiliation></author><author><name sortKey="Siemens, Nikolai" sort="Siemens, Nikolai" uniqKey="Siemens N" first="Nikolai" last="Siemens">Nikolai Siemens</name><affiliation wicri:level="1"><nlm:affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86</wicri:regionArea><wicri:noRegion>141 86</wicri:noRegion></affiliation></author><author><name sortKey="Monk, Ian R" sort="Monk, Ian R" uniqKey="Monk I" first="Ian R" last="Monk">Ian R. 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sort="Siemens, Nikolai" uniqKey="Siemens N" first="Nikolai" last="Siemens">Nikolai Siemens</name><affiliation wicri:level="1"><nlm:affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86</wicri:regionArea><wicri:noRegion>141 86</wicri:noRegion></affiliation></author><author><name sortKey="Monk, Ian R" sort="Monk, Ian R" uniqKey="Monk I" first="Ian R" last="Monk">Ian R. Monk</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Mohan, Disha B" sort="Mohan, Disha B" uniqKey="Mohan D" first="Disha B" last="Mohan">Disha B. Mohan</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012</wicri:regionArea><wicri:noRegion>560012</wicri:noRegion></affiliation></author><author><name sortKey="Mukundan, Santhosh" sort="Mukundan, Santhosh" uniqKey="Mukundan S" first="Santhosh" last="Mukundan">Santhosh Mukundan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Basic Sciences, School of Medicine and Health Sciences, University of North, Dakota, ND, 58202-9037, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Basic Sciences, School of Medicine and Health Sciences, University of North, Dakota, ND, 58202-9037</wicri:regionArea><wicri:noRegion>58202-9037</wicri:noRegion></affiliation></author><author><name sortKey="Krishnan, Karthickeyan Chella" sort="Krishnan, Karthickeyan Chella" uniqKey="Krishnan K" first="Karthickeyan Chella" last="Krishnan">Karthickeyan Chella Krishnan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Basic Sciences, School of Medicine and Health Sciences, University of North, Dakota, ND, 58202-9037, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Basic Sciences, School of Medicine and Health Sciences, University of North, Dakota, ND, 58202-9037</wicri:regionArea><wicri:noRegion>58202-9037</wicri:noRegion></affiliation></author><author><name sortKey="Prabhakara, Sushma" sort="Prabhakara, Sushma" uniqKey="Prabhakara S" first="Sushma" last="Prabhakara">Sushma Prabhakara</name><affiliation wicri:level="1"><nlm:affiliation>Society for Innovation and Development, Indian Institute of Science, Bangalore, 560012, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Society for Innovation and Development, Indian Institute of Science, Bangalore, 560012</wicri:regionArea><wicri:noRegion>560012</wicri:noRegion></affiliation></author><author><name sortKey="Sn Ll, Johanna" sort="Sn Ll, Johanna" uniqKey="Sn Ll J" first="Johanna" last="Sn Ll">Johanna Sn Ll</name><affiliation wicri:level="1"><nlm:affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86</wicri:regionArea><wicri:noRegion>141 86</wicri:noRegion></affiliation></author><author><name sortKey="Kearns, Angela" sort="Kearns, Angela" uniqKey="Kearns A" first="Angela" last="Kearns">Angela Kearns</name><affiliation wicri:level="1"><nlm:affiliation>National Infection Service, Public Health England (PHE), Colindale, London, NW95EQ, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Infection Service, Public Health England (PHE), Colindale, London, NW95EQ</wicri:regionArea><wicri:noRegion>NW95EQ</wicri:noRegion></affiliation></author><author><name sortKey="Vandenesch, Francois" sort="Vandenesch, Francois" uniqKey="Vandenesch F" first="Francois" last="Vandenesch">Francois Vandenesch</name><affiliation><nlm:affiliation>CIRI, International Center for Infectiology Research, Inserm, U1111, CNRS UMR5308, Université Lyon 1, École Normale, Supérieure de Lyon, French.</nlm:affiliation><wicri:noCountry code="subField">French</wicri:noCountry></affiliation></author><author><name sortKey="Svensson, Mattias" sort="Svensson, Mattias" uniqKey="Svensson M" first="Mattias" last="Svensson">Mattias Svensson</name><affiliation wicri:level="1"><nlm:affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86</wicri:regionArea><wicri:noRegion>141 86</wicri:noRegion></affiliation></author><author><name sortKey="Kotb, Malak" sort="Kotb, Malak" uniqKey="Kotb M" first="Malak" last="Kotb">Malak Kotb</name><affiliation wicri:level="1"><nlm:affiliation>Department of Basic Sciences, School of Medicine and Health Sciences, University of North, Dakota, ND, 58202-9037, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Basic Sciences, School of Medicine and Health Sciences, University of North, Dakota, ND, 58202-9037</wicri:regionArea><wicri:noRegion>58202-9037</wicri:noRegion></affiliation></author><author><name sortKey="Gopal, Balasubramanian" sort="Gopal, Balasubramanian" uniqKey="Gopal B" first="Balasubramanian" last="Gopal">Balasubramanian Gopal</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012</wicri:regionArea><wicri:noRegion>560012</wicri:noRegion></affiliation></author><author><name sortKey="Arakere, Gayathri" sort="Arakere, Gayathri" uniqKey="Arakere G" first="Gayathri" last="Arakere">Gayathri Arakere</name><affiliation wicri:level="1"><nlm:affiliation>Society for Innovation and Development, Indian Institute of Science, Bangalore, 560012, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Society for Innovation and Development, Indian Institute of Science, Bangalore, 560012</wicri:regionArea><wicri:noRegion>560012</wicri:noRegion></affiliation></author><author><name sortKey="Norrby Teglund, Anna" sort="Norrby Teglund, Anna" uniqKey="Norrby Teglund A" first="Anna" last="Norrby-Teglund">Anna Norrby-Teglund</name><affiliation wicri:level="1"><nlm:affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86</wicri:regionArea><wicri:noRegion>141 86</wicri:noRegion></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections. One of the highly successful and rapidly disseminating clones is MRSA ST22 commonly associated with skin tropism. Here we show that a naturally occurring single amino acid substitution (tyrosine to cysteine) at position 223 of AgrC determines starkly different ST22 S. aureus virulence phenotypes, e.g. cytotoxic or colonizing, as evident in both in vitro and in vivo skin infections. Y223C amino acid substitution destabilizes AgrC-AgrA interaction leading to a colonizing phenotype characterized by upregulation of bacterial surface proteins. The colonizing phenotype strains cause less severe skin tissue damage, show decreased susceptibility towards the antimicrobial LL-37 and induce autophagy. In contrast, cytotoxic strains with tyrosine at position 223 of AgrC cause infections characterized by inflammasome activation and severe skin tissue pathology. Taken together, the study demonstrates how a single amino acid substitution in the histidine kinase receptor AgrC of ST22 strains determines virulence properties and infection outcome.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">27511873</PMID><DateCreated><Year>2016</Year><Month>08</Month><Day>11</Day></DateCreated><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>6</Volume><PubDate><Year>2016</Year><Month>Aug</Month><Day>11</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains.</ArticleTitle><Pagination><MedlinePgn>31360</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/srep31360</ELocationID><Abstract><AbstractText>Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections. One of the highly successful and rapidly disseminating clones is MRSA ST22 commonly associated with skin tropism. Here we show that a naturally occurring single amino acid substitution (tyrosine to cysteine) at position 223 of AgrC determines starkly different ST22 S. aureus virulence phenotypes, e.g. cytotoxic or colonizing, as evident in both in vitro and in vivo skin infections. Y223C amino acid substitution destabilizes AgrC-AgrA interaction leading to a colonizing phenotype characterized by upregulation of bacterial surface proteins. The colonizing phenotype strains cause less severe skin tissue damage, show decreased susceptibility towards the antimicrobial LL-37 and induce autophagy. In contrast, cytotoxic strains with tyrosine at position 223 of AgrC cause infections characterized by inflammasome activation and severe skin tissue pathology. Taken together, the study demonstrates how a single amino acid substitution in the histidine kinase receptor AgrC of ST22 strains determines virulence properties and infection outcome.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mairpady Shambat</LastName><ForeName>Srikanth</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Siemens</LastName><ForeName>Nikolai</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Monk</LastName><ForeName>Ian R</ForeName><Initials>IR</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Melbourne, Victoria, 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mohan</LastName><ForeName>Disha B</ForeName><Initials>DB</Initials><AffiliationInfo><Affiliation>Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mukundan</LastName><ForeName>Santhosh</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Basic Sciences, School of Medicine and Health Sciences, University of North, Dakota, ND, 58202-9037, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Krishnan</LastName><ForeName>Karthickeyan Chella</ForeName><Initials>KC</Initials><AffiliationInfo><Affiliation>Department of Basic Sciences, School of Medicine and Health Sciences, University of North, Dakota, ND, 58202-9037, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prabhakara</LastName><ForeName>Sushma</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Society for Innovation and Development, Indian Institute of Science, Bangalore, 560012, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Snäll</LastName><ForeName>Johanna</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kearns</LastName><ForeName>Angela</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>National Infection Service, Public Health England (PHE), Colindale, London, NW95EQ, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vandenesch</LastName><ForeName>Francois</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>CIRI, International Center for Infectiology Research, Inserm, U1111, CNRS UMR5308, Université Lyon 1, École Normale, Supérieure de Lyon, French.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>French National Reference Center for Staphylococci, Hospices Civils de Lyon, 69677, Bron Cedex, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Svensson</LastName><ForeName>Mattias</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kotb</LastName><ForeName>Malak</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Basic Sciences, School of Medicine and Health Sciences, University of North, Dakota, ND, 58202-9037, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gopal</LastName><ForeName>Balasubramanian</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arakere</LastName><ForeName>Gayathri</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Society for Innovation and Development, Indian Institute of Science, Bangalore, 560012, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Norrby-Teglund</LastName><ForeName>Anna</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Karolinska Institutet, Center for Infectious Medicine, Karolinska University Hospital Huddinge, 141 86, Sweden.</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>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci 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Source="NLM">PMC4980769</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>05</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>07</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>8</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>8</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>8</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27511873</ArticleId><ArticleId IdType="pii">srep31360</ArticleId><ArticleId IdType="doi">10.1038/srep31360</ArticleId><ArticleId IdType="pmc">PMC4980769</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>Inde</li><li>Royaume-Uni</li><li>Suède</li><li>États-Unis</li></country><region><li>Victoria (État)</li></region><settlement><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><noCountry><name sortKey="Vandenesch, Francois" sort="Vandenesch, Francois" uniqKey="Vandenesch F" first="Francois" last="Vandenesch">Francois Vandenesch</name></noCountry><country name="Suède"><noRegion><name sortKey="Mairpady Shambat, Srikanth" sort="Mairpady Shambat, Srikanth" uniqKey="Mairpady Shambat S" first="Srikanth" last="Mairpady Shambat">Srikanth Mairpady Shambat</name></noRegion><name sortKey="Norrby Teglund, Anna" sort="Norrby Teglund, Anna" uniqKey="Norrby Teglund A" first="Anna" last="Norrby-Teglund">Anna Norrby-Teglund</name><name sortKey="Siemens, Nikolai" sort="Siemens, Nikolai" uniqKey="Siemens N" first="Nikolai" last="Siemens">Nikolai Siemens</name><name sortKey="Sn Ll, Johanna" sort="Sn Ll, Johanna" uniqKey="Sn Ll J" first="Johanna" last="Sn Ll">Johanna Sn Ll</name><name sortKey="Svensson, Mattias" sort="Svensson, Mattias" uniqKey="Svensson M" first="Mattias" last="Svensson">Mattias Svensson</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Monk, Ian R" sort="Monk, Ian R" uniqKey="Monk I" first="Ian R" last="Monk">Ian R. Monk</name></region></country><country name="Inde"><noRegion><name sortKey="Mohan, Disha B" sort="Mohan, Disha B" uniqKey="Mohan D" first="Disha B" last="Mohan">Disha B. Mohan</name></noRegion><name sortKey="Arakere, Gayathri" sort="Arakere, Gayathri" uniqKey="Arakere G" first="Gayathri" last="Arakere">Gayathri Arakere</name><name sortKey="Gopal, Balasubramanian" sort="Gopal, Balasubramanian" uniqKey="Gopal B" first="Balasubramanian" last="Gopal">Balasubramanian Gopal</name><name sortKey="Prabhakara, Sushma" sort="Prabhakara, Sushma" uniqKey="Prabhakara S" first="Sushma" last="Prabhakara">Sushma Prabhakara</name></country><country name="États-Unis"><noRegion><name sortKey="Mukundan, Santhosh" sort="Mukundan, Santhosh" uniqKey="Mukundan S" first="Santhosh" last="Mukundan">Santhosh Mukundan</name></noRegion><name sortKey="Kotb, Malak" sort="Kotb, Malak" uniqKey="Kotb M" first="Malak" last="Kotb">Malak Kotb</name><name sortKey="Krishnan, Karthickeyan Chella" sort="Krishnan, Karthickeyan Chella" uniqKey="Krishnan K" first="Karthickeyan Chella" last="Krishnan">Karthickeyan Chella Krishnan</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Kearns, Angela" sort="Kearns, Angela" uniqKey="Kearns A" first="Angela" last="Kearns">Angela Kearns</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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