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Bacteriomimetic invasin-functionalized nanocarriers for intracellular delivery.

Identifieur interne : 001759 ( Main/Exploration ); précédent : 001758; suivant : 001760

Bacteriomimetic invasin-functionalized nanocarriers for intracellular delivery.

Auteurs : Hagar Ibrahim Labouta [Égypte] ; Sara Menina [Allemagne] ; Annika Kochut [Allemagne] ; Sarah Gordon [Allemagne] ; Rebecca Geyer [Allemagne] ; Petra Dersch [Allemagne] ; Claus-Michael Lehr [Allemagne]

Source :

RBID : pubmed:26522071

Descripteurs français

English descriptors

Abstract

Intracellular bacteria invade mammalian cells to establish an infectious niche. The current work models adhesion and subsequent internalization strategy of pathogenic bacteria into mammalian cells to design a bacteriomimetic bioinvasive delivery system. We report on the surface functionalization of liposomes with a C-terminal fragment of invasin (InvA497), an invasion factor in the outer membrane of Yersinia pseudotuberculosis. InvA497-functionalized liposomes adhere to mammalian epithelial HEp-2 cell line at different infection stages with a significantly higher efficiency than liposomes functionalized with bovine serum albumin. Covalent attachment of InvA497 results in higher cellular adhesion than liposomes with physically adsorbed InvA497 with non-specific surface protein alignment. Uptake studies in HEp-2 cells indicate active internalization of InvA497-functionalized liposomes via β1-integrin receptor-mediated uptake mechanism mimicking the natural invasion strategy of Y. pseudotuberculosis. Uptake studies in Caco-2 cells at different polarization states demonstrate specific targeting of the InvA497-functionalized liposomes to less polarized cells reflecting the status of inflamed cells. Moreover, when loaded with the anti-infective agent gentamicin and applied to HEp-2 cells infected with Y. pseudotuberculosis, InvA497-functionalized liposomes are able to significantly reduce the infection load relative to non-functionalized drug-loaded liposomes. This indicates a promising application of such a bacteriomimetic system for drug delivery to intracellular compartments.

DOI: 10.1016/j.jconrel.2015.10.052
PubMed: 26522071


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Le document en format XML

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<term>Adhesins, Bacterial (chemistry)</term>
<term>Adhesins, Bacterial (metabolism)</term>
<term>Anti-Bacterial Agents (chemistry)</term>
<term>Anti-Bacterial Agents (metabolism)</term>
<term>Anti-Bacterial Agents (pharmacology)</term>
<term>Bacterial Adhesion (MeSH)</term>
<term>Bacterial Load (drug effects)</term>
<term>Biological Transport (MeSH)</term>
<term>Biomimetics (MeSH)</term>
<term>Caco-2 Cells (MeSH)</term>
<term>Cell Membrane (drug effects)</term>
<term>Cell Membrane (metabolism)</term>
<term>Cell Membrane (microbiology)</term>
<term>Drug Carriers (MeSH)</term>
<term>Epithelial Cells (drug effects)</term>
<term>Epithelial Cells (metabolism)</term>
<term>Epithelial Cells (microbiology)</term>
<term>Gentamicins (chemistry)</term>
<term>Gentamicins (metabolism)</term>
<term>Gentamicins (pharmacology)</term>
<term>Humans (MeSH)</term>
<term>Integrin beta1 (MeSH)</term>
<term>Kinetics (MeSH)</term>
<term>Liposomes (MeSH)</term>
<term>Nanoparticles (MeSH)</term>
<term>Nanotechnology (MeSH)</term>
<term>Peptide Fragments (chemistry)</term>
<term>Peptide Fragments (metabolism)</term>
<term>Yersinia pseudotuberculosis (drug effects)</term>
<term>Yersinia pseudotuberculosis (metabolism)</term>
<term>Yersinia pseudotuberculosis (pathogenicity)</term>
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<term>Adhérence bactérienne (MeSH)</term>
<term>Adhésines bactériennes (composition chimique)</term>
<term>Adhésines bactériennes (métabolisme)</term>
<term>Antibactériens (composition chimique)</term>
<term>Antibactériens (métabolisme)</term>
<term>Antibactériens (pharmacologie)</term>
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<term>Cellules épithéliales (microbiologie)</term>
<term>Cellules épithéliales (métabolisme)</term>
<term>Charge bactérienne (effets des médicaments et des substances chimiques)</term>
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<term>Fragments peptidiques (métabolisme)</term>
<term>Gentamicine (composition chimique)</term>
<term>Gentamicine (métabolisme)</term>
<term>Gentamicine (pharmacologie)</term>
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<term>Liposomes (MeSH)</term>
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<term>Membrane cellulaire (microbiologie)</term>
<term>Membrane cellulaire (métabolisme)</term>
<term>Nanoparticules (MeSH)</term>
<term>Nanotechnologie (MeSH)</term>
<term>Transport biologique (MeSH)</term>
<term>Vecteurs de médicaments (MeSH)</term>
<term>Yersinia pseudotuberculosis (effets des médicaments et des substances chimiques)</term>
<term>Yersinia pseudotuberculosis (métabolisme)</term>
<term>Yersinia pseudotuberculosis (pathogénicité)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Adhesins, Bacterial</term>
<term>Anti-Bacterial Agents</term>
<term>Gentamicins</term>
<term>Peptide Fragments</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Adhesins, Bacterial</term>
<term>Anti-Bacterial Agents</term>
<term>Gentamicins</term>
<term>Peptide Fragments</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Anti-Bacterial Agents</term>
<term>Gentamicins</term>
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<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr">
<term>Adhésines bactériennes</term>
<term>Antibactériens</term>
<term>Fragments peptidiques</term>
<term>Gentamicine</term>
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<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Bacterial Load</term>
<term>Cell Membrane</term>
<term>Epithelial Cells</term>
<term>Yersinia pseudotuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr">
<term>Cellules épithéliales</term>
<term>Charge bactérienne</term>
<term>Membrane cellulaire</term>
<term>Yersinia pseudotuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Cell Membrane</term>
<term>Epithelial Cells</term>
<term>Yersinia pseudotuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr">
<term>Cellules épithéliales</term>
<term>Membrane cellulaire</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en">
<term>Cell Membrane</term>
<term>Epithelial Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Adhésines bactériennes</term>
<term>Antibactériens</term>
<term>Cellules épithéliales</term>
<term>Fragments peptidiques</term>
<term>Gentamicine</term>
<term>Membrane cellulaire</term>
<term>Yersinia pseudotuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en">
<term>Yersinia pseudotuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr">
<term>Yersinia pseudotuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Antibactériens</term>
<term>Gentamicine</term>
</keywords>
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<term>Bacterial Adhesion</term>
<term>Biological Transport</term>
<term>Biomimetics</term>
<term>Caco-2 Cells</term>
<term>Drug Carriers</term>
<term>Humans</term>
<term>Integrin beta1</term>
<term>Kinetics</term>
<term>Liposomes</term>
<term>Nanoparticles</term>
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<term>Cinétique</term>
<term>Humains</term>
<term>Liposomes</term>
<term>Nanoparticules</term>
<term>Nanotechnologie</term>
<term>Transport biologique</term>
<term>Vecteurs de médicaments</term>
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<front>
<div type="abstract" xml:lang="en">Intracellular bacteria invade mammalian cells to establish an infectious niche. The current work models adhesion and subsequent internalization strategy of pathogenic bacteria into mammalian cells to design a bacteriomimetic bioinvasive delivery system. We report on the surface functionalization of liposomes with a C-terminal fragment of invasin (InvA497), an invasion factor in the outer membrane of Yersinia pseudotuberculosis. InvA497-functionalized liposomes adhere to mammalian epithelial HEp-2 cell line at different infection stages with a significantly higher efficiency than liposomes functionalized with bovine serum albumin. Covalent attachment of InvA497 results in higher cellular adhesion than liposomes with physically adsorbed InvA497 with non-specific surface protein alignment. Uptake studies in HEp-2 cells indicate active internalization of InvA497-functionalized liposomes via β1-integrin receptor-mediated uptake mechanism mimicking the natural invasion strategy of Y. pseudotuberculosis. Uptake studies in Caco-2 cells at different polarization states demonstrate specific targeting of the InvA497-functionalized liposomes to less polarized cells reflecting the status of inflamed cells. Moreover, when loaded with the anti-infective agent gentamicin and applied to HEp-2 cells infected with Y. pseudotuberculosis, InvA497-functionalized liposomes are able to significantly reduce the infection load relative to non-functionalized drug-loaded liposomes. This indicates a promising application of such a bacteriomimetic system for drug delivery to intracellular compartments. </div>
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<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jconrel.2015.10.052</ELocationID>
<Abstract>
<AbstractText>Intracellular bacteria invade mammalian cells to establish an infectious niche. The current work models adhesion and subsequent internalization strategy of pathogenic bacteria into mammalian cells to design a bacteriomimetic bioinvasive delivery system. We report on the surface functionalization of liposomes with a C-terminal fragment of invasin (InvA497), an invasion factor in the outer membrane of Yersinia pseudotuberculosis. InvA497-functionalized liposomes adhere to mammalian epithelial HEp-2 cell line at different infection stages with a significantly higher efficiency than liposomes functionalized with bovine serum albumin. Covalent attachment of InvA497 results in higher cellular adhesion than liposomes with physically adsorbed InvA497 with non-specific surface protein alignment. Uptake studies in HEp-2 cells indicate active internalization of InvA497-functionalized liposomes via β1-integrin receptor-mediated uptake mechanism mimicking the natural invasion strategy of Y. pseudotuberculosis. Uptake studies in Caco-2 cells at different polarization states demonstrate specific targeting of the InvA497-functionalized liposomes to less polarized cells reflecting the status of inflamed cells. Moreover, when loaded with the anti-infective agent gentamicin and applied to HEp-2 cells infected with Y. pseudotuberculosis, InvA497-functionalized liposomes are able to significantly reduce the infection load relative to non-functionalized drug-loaded liposomes. This indicates a promising application of such a bacteriomimetic system for drug delivery to intracellular compartments. </AbstractText>
<CopyrightInformation>Copyright © 2015 Elsevier B.V. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Labouta</LastName>
<ForeName>Hagar Ibrahim</ForeName>
<Initials>HI</Initials>
<AffiliationInfo>
<Affiliation>Dept. of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Campus A4 1, D-66123 Saarbrücken, Germany; Department of Pharmaceutics, Alexandria University, Alexandria 21521, Egypt.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Menina</LastName>
<ForeName>Sara</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Dept. of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Campus A4 1, D-66123 Saarbrücken, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kochut</LastName>
<ForeName>Annika</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Gordon</LastName>
<ForeName>Sarah</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Dept. of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Campus A4 1, D-66123 Saarbrücken, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Geyer</LastName>
<ForeName>Rebecca</ForeName>
<Initials>R</Initials>
<AffiliationInfo>
<Affiliation>Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Dersch</LastName>
<ForeName>Petra</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lehr</LastName>
<ForeName>Claus-Michael</ForeName>
<Initials>CM</Initials>
<AffiliationInfo>
<Affiliation>Dept. of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Campus A4 1, D-66123 Saarbrücken, Germany; Department of Pharmacy, Saarland University, D-66123 Saarbrücken, Germany. Electronic address: Claus-Michael.Lehr@helmholtz-hzi.de.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2015</Year>
<Month>10</Month>
<Day>29</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>Netherlands</Country>
<MedlineTA>J Control Release</MedlineTA>
<NlmUniqueID>8607908</NlmUniqueID>
<ISSNLinking>0168-3659</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D018829">Adhesins, Bacterial</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004337">Drug Carriers</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D005839">Gentamicins</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D019012">Integrin beta1</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D008081">Liposomes</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D010446">Peptide Fragments</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>114073-91-5</RegistryNumber>
<NameOfSubstance UI="C053476">invasin, Yersinia</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D018829" MajorTopicYN="N">Adhesins, Bacterial</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D001422" MajorTopicYN="N">Bacterial Adhesion</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D058491" MajorTopicYN="N">Bacterial Load</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D001692" MajorTopicYN="N">Biological Transport</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D032701" MajorTopicYN="N">Biomimetics</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D018938" MajorTopicYN="N">Caco-2 Cells</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D002462" MajorTopicYN="N">Cell Membrane</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004337" MajorTopicYN="Y">Drug Carriers</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004847" MajorTopicYN="N">Epithelial Cells</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005839" MajorTopicYN="N">Gentamicins</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D019012" MajorTopicYN="N">Integrin beta1</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007700" MajorTopicYN="N">Kinetics</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008081" MajorTopicYN="N">Liposomes</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D053758" MajorTopicYN="Y">Nanoparticles</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D036103" MajorTopicYN="N">Nanotechnology</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010446" MajorTopicYN="N">Peptide Fragments</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015011" MajorTopicYN="N">Yersinia pseudotuberculosis</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">Bacteriomimetic liposomes</Keyword>
<Keyword MajorTopicYN="N">Bioinvasive carriers</Keyword>
<Keyword MajorTopicYN="N">Cell uptake kinetics</Keyword>
<Keyword MajorTopicYN="N">Intracellular delivery</Keyword>
<Keyword MajorTopicYN="N">Receptor competition experiments</Keyword>
</KeywordList>
</MedlineCitation>
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<PubMedPubDate PubStatus="received">
<Year>2015</Year>
<Month>10</Month>
<Day>01</Day>
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<PubMedPubDate PubStatus="revised">
<Year>2015</Year>
<Month>10</Month>
<Day>26</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2015</Year>
<Month>10</Month>
<Day>28</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2015</Year>
<Month>11</Month>
<Day>3</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<Month>11</Month>
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</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2017</Year>
<Month>1</Month>
<Day>11</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">26522071</ArticleId>
<ArticleId IdType="pii">S0168-3659(15)30218-2</ArticleId>
<ArticleId IdType="doi">10.1016/j.jconrel.2015.10.052</ArticleId>
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</pubmed>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>Égypte</li>
</country>
<region>
<li>Sarre (Land)</li>
</region>
<settlement>
<li>Sarrebruck</li>
</settlement>
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<tree>
<country name="Égypte">
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<name sortKey="Labouta, Hagar Ibrahim" sort="Labouta, Hagar Ibrahim" uniqKey="Labouta H" first="Hagar Ibrahim" last="Labouta">Hagar Ibrahim Labouta</name>
</noRegion>
</country>
<country name="Allemagne">
<region name="Sarre (Land)">
<name sortKey="Menina, Sara" sort="Menina, Sara" uniqKey="Menina S" first="Sara" last="Menina">Sara Menina</name>
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<name sortKey="Dersch, Petra" sort="Dersch, Petra" uniqKey="Dersch P" first="Petra" last="Dersch">Petra Dersch</name>
<name sortKey="Geyer, Rebecca" sort="Geyer, Rebecca" uniqKey="Geyer R" first="Rebecca" last="Geyer">Rebecca Geyer</name>
<name sortKey="Gordon, Sarah" sort="Gordon, Sarah" uniqKey="Gordon S" first="Sarah" last="Gordon">Sarah Gordon</name>
<name sortKey="Kochut, Annika" sort="Kochut, Annika" uniqKey="Kochut A" first="Annika" last="Kochut">Annika Kochut</name>
<name sortKey="Lehr, Claus Michael" sort="Lehr, Claus Michael" uniqKey="Lehr C" first="Claus-Michael" last="Lehr">Claus-Michael Lehr</name>
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