RapamycinFungusV1, Main, Exploration, bibRecord, 000718

The Macrolide Toxin Mycolactone Promotes Bim-Dependent Apoptosis in Buruli Ulcer through Inhibition of mTOR.

Identifieur interne : 000718 ( Main/Exploration ); précédent : 000717; suivant : 000719

The Macrolide Toxin Mycolactone Promotes Bim-Dependent Apoptosis in Buruli Ulcer through Inhibition of mTOR.

Auteurs : Raphael Bieri [Suisse] ; Nicole Scherr [Suisse] ; Marie-Thérèse Ruf [Suisse] ; Jean-Pierre Dangy [Suisse] ; Philipp Gersbach [Suisse] ; Matthias Gehringer [Suisse] ; Karl-Heinz Altmann [Suisse] ; Gerd Pluschke [Suisse]

Source :

ACS chemical biology [ 1554-8937 ] ; 2017.

RBID : pubmed:28294596

Descripteurs français

KwdFr :
- Animaux (MeSH), Apoptose (MeSH), Cellules cultivées (MeSH), Complexe-1 cible mécanistique de la rapamycine (MeSH), Complexe-2 cible mécanistique de la rapamycine (MeSH), Complexes multiprotéiques (effets des médicaments et des substances chimiques), Macrolides (pharmacologie), Macrolides (toxicité), Mycobacterium ulcerans (composition chimique), Mycobacterium ulcerans (pathogénicité), Protéine-11 analogue à Bcl-2 (génétique), Protéine-11 analogue à Bcl-2 (métabolisme), Protéine-11 analogue à Bcl-2 (physiologie), Souris (MeSH), Sérine-thréonine kinases TOR (antagonistes et inhibiteurs), Sérine-thréonine kinases TOR (effets des médicaments et des substances chimiques), Techniques de knock-out de gènes (MeSH), Ulcère de Buruli (anatomopathologie), Ulcère de Buruli (microbiologie).
MESH :
- anatomopathologie : Ulcère de Buruli.
- antagonistes et inhibiteurs : Sérine-thréonine kinases TOR.
- composition chimique : Mycobacterium ulcerans.
- effets des médicaments et des substances chimiques : Complexes multiprotéiques, Sérine-thréonine kinases TOR.
- génétique : Protéine-11 analogue à Bcl-2.
- microbiologie : Ulcère de Buruli.
- métabolisme : Protéine-11 analogue à Bcl-2.
- pathogénicité : Mycobacterium ulcerans.
- pharmacologie : Macrolides.
- physiologie : Protéine-11 analogue à Bcl-2.
- toxicité : Macrolides.
- Animaux, Apoptose, Cellules cultivées, Complexe-1 cible mécanistique de la rapamycine, Complexe-2 cible mécanistique de la rapamycine, Souris, Techniques de knock-out de gènes.

English descriptors

KwdEn :
- Animals (MeSH), Apoptosis (MeSH), Bcl-2-Like Protein 11 (genetics), Bcl-2-Like Protein 11 (metabolism), Bcl-2-Like Protein 11 (physiology), Buruli Ulcer (microbiology), Buruli Ulcer (pathology), Cells, Cultured (MeSH), Gene Knockout Techniques (MeSH), Macrolides (pharmacology), Macrolides (toxicity), Mechanistic Target of Rapamycin Complex 1 (MeSH), Mechanistic Target of Rapamycin Complex 2 (MeSH), Mice (MeSH), Multiprotein Complexes (drug effects), Mycobacterium ulcerans (chemistry), Mycobacterium ulcerans (pathogenicity), TOR Serine-Threonine Kinases (antagonists & inhibitors), TOR Serine-Threonine Kinases (drug effects).
MESH :
- chemical , antagonists & inhibitors : TOR Serine-Threonine Kinases.
- chemical , drug effects : Multiprotein Complexes, TOR Serine-Threonine Kinases.
- chemical , genetics : Bcl-2-Like Protein 11.
- chemical , metabolism : Bcl-2-Like Protein 11.
- chemical , pharmacology : Macrolides.
- chemical , physiology : Bcl-2-Like Protein 11.
- chemistry : Mycobacterium ulcerans.
- microbiology : Buruli Ulcer.
- pathogenicity : Mycobacterium ulcerans.
- pathology : Buruli Ulcer.
- chemical , toxicity : Macrolides.
- Animals, Apoptosis, Cells, Cultured, Gene Knockout Techniques, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Mice.

Abstract

Mycolactone, the macrolide exotoxin produced by Mycobacterium ulcerans, is central to the pathogenesis of the chronic necrotizing skin disease Buruli ulcer (BU). Here we show that mycolactone acts as an inhibitor of the mechanistic Target of Rapamycin (mTOR) signaling pathway by interfering with the assembly of the two distinct mTOR protein complexes mTORC1 and mTORC2, which regulate different cellular processes. Inhibition of the assembly of the rictor containing mTORC2 complex by mycolactone prevents phosphorylation of the serine/threonine protein kinase Akt. The associated inactivation of Akt leads to the dephosphorylation and activation of the Akt-targeted transcription factor FoxO3. Subsequent up-regulation of the FoxO3 target gene BCL2L11 (Bim) increases expression of the pro-apoptotic regulator Bim, driving mycolactone treated mammalian cells into apoptosis. The central role of Bim-dependent apoptosis in BU pathogenesis deduced from our experiments with cultured mammalian cells was further verified in an experimental M. ulcerans infection model. As predicted by the model, M. ulcerans infected Bim knockout mice did not develop necrotic BU lesions with large clusters of extracellular bacteria, but were able to contain the mycobacterial multiplication. Our findings provide a new coherent and comprehensive concept of BU pathogenesis.

DOI: 10.1021/acschembio.7b00053
PubMed: 28294596

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000847
to stream Main, to step Curation: 000847

Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>Apoptosis (MeSH)</term>
<term>Bcl-2-Like Protein 11 (genetics)</term>
<term>Bcl-2-Like Protein 11 (metabolism)</term>
<term>Bcl-2-Like Protein 11 (physiology)</term>
<term>Buruli Ulcer (microbiology)</term>
<term>Buruli Ulcer (pathology)</term>
<term>Cells, Cultured (MeSH)</term>
<term>Gene Knockout Techniques (MeSH)</term>
<term>Macrolides (pharmacology)</term>
<term>Macrolides (toxicity)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (MeSH)</term>
<term>Mechanistic Target of Rapamycin Complex 2 (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Multiprotein Complexes (drug effects)</term>
<term>Mycobacterium ulcerans (chemistry)</term>
<term>Mycobacterium ulcerans (pathogenicity)</term>
<term>TOR Serine-Threonine Kinases (antagonists & inhibitors)</term>
<term>TOR Serine-Threonine Kinases (drug effects)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Apoptose (MeSH)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (MeSH)</term>
<term>Complexe-2 cible mécanistique de la rapamycine (MeSH)</term>
<term>Complexes multiprotéiques (effets des médicaments et des substances chimiques)</term>
<term>Macrolides (pharmacologie)</term>
<term>Macrolides (toxicité)</term>
<term>Mycobacterium ulcerans (composition chimique)</term>
<term>Mycobacterium ulcerans (pathogénicité)</term>
<term>Protéine-11 analogue à Bcl-2 (génétique)</term>
<term>Protéine-11 analogue à Bcl-2 (métabolisme)</term>
<term>Protéine-11 analogue à Bcl-2 (physiologie)</term>
<term>Souris (MeSH)</term>
<term>Sérine-thréonine kinases TOR (antagonistes et inhibiteurs)</term>
<term>Sérine-thréonine kinases TOR (effets des médicaments et des substances chimiques)</term>
<term>Techniques de knock-out de gènes (MeSH)</term>
<term>Ulcère de Buruli (anatomopathologie)</term>
<term>Ulcère de Buruli (microbiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Multiprotein Complexes</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Bcl-2-Like Protein 11</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Bcl-2-Like Protein 11</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Macrolides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Bcl-2-Like Protein 11</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Ulcère de Buruli</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Mycobacterium ulcerans</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Mycobacterium ulcerans</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Complexes multiprotéiques</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéine-11 analogue à Bcl-2</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Ulcère de Buruli</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Buruli Ulcer</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéine-11 analogue à Bcl-2</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Mycobacterium ulcerans</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Mycobacterium ulcerans</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Buruli Ulcer</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Macrolides</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Protéine-11 analogue à Bcl-2</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Macrolides</term>
</keywords>
<keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Macrolides</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Apoptosis</term>
<term>Cells, Cultured</term>
<term>Gene Knockout Techniques</term>
<term>Mechanistic Target of Rapamycin Complex 1</term>
<term>Mechanistic Target of Rapamycin Complex 2</term>
<term>Mice</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Apoptose</term>
<term>Cellules cultivées</term>
<term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Complexe-2 cible mécanistique de la rapamycine</term>
<term>Souris</term>
<term>Techniques de knock-out de gènes</term>
</keywords>
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<front><div type="abstract" xml:lang="en">Mycolactone, the macrolide exotoxin produced by Mycobacterium ulcerans, is central to the pathogenesis of the chronic necrotizing skin disease Buruli ulcer (BU). Here we show that mycolactone acts as an inhibitor of the mechanistic Target of Rapamycin (mTOR) signaling pathway by interfering with the assembly of the two distinct mTOR protein complexes mTORC1 and mTORC2, which regulate different cellular processes. Inhibition of the assembly of the rictor containing mTORC2 complex by mycolactone prevents phosphorylation of the serine/threonine protein kinase Akt. The associated inactivation of Akt leads to the dephosphorylation and activation of the Akt-targeted transcription factor FoxO3. Subsequent up-regulation of the FoxO3 target gene BCL2L11 (Bim) increases expression of the pro-apoptotic regulator Bim, driving mycolactone treated mammalian cells into apoptosis. The central role of Bim-dependent apoptosis in BU pathogenesis deduced from our experiments with cultured mammalian cells was further verified in an experimental M. ulcerans infection model. As predicted by the model, M. ulcerans infected Bim knockout mice did not develop necrotic BU lesions with large clusters of extracellular bacteria, but were able to contain the mycobacterial multiplication. Our findings provide a new coherent and comprehensive concept of BU pathogenesis.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28294596</PMID>
<DateCompleted><Year>2017</Year>
<Month>09</Month>
<Day>12</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>02</Month>
<Day>01</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1554-8937</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>12</Volume>
<Issue>5</Issue>
<PubDate><Year>2017</Year>
<Month>05</Month>
<Day>19</Day>
</PubDate>
</JournalIssue>
<Title>ACS chemical biology</Title>
<ISOAbbreviation>ACS Chem Biol</ISOAbbreviation>
</Journal>
<ArticleTitle>The Macrolide Toxin Mycolactone Promotes Bim-Dependent Apoptosis in Buruli Ulcer through Inhibition of mTOR.</ArticleTitle>
<Pagination><MedlinePgn>1297-1307</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1021/acschembio.7b00053</ELocationID>
<Abstract><AbstractText>Mycolactone, the macrolide exotoxin produced by Mycobacterium ulcerans, is central to the pathogenesis of the chronic necrotizing skin disease Buruli ulcer (BU). Here we show that mycolactone acts as an inhibitor of the mechanistic Target of Rapamycin (mTOR) signaling pathway by interfering with the assembly of the two distinct mTOR protein complexes mTORC1 and mTORC2, which regulate different cellular processes. Inhibition of the assembly of the rictor containing mTORC2 complex by mycolactone prevents phosphorylation of the serine/threonine protein kinase Akt. The associated inactivation of Akt leads to the dephosphorylation and activation of the Akt-targeted transcription factor FoxO3. Subsequent up-regulation of the FoxO3 target gene BCL2L11 (Bim) increases expression of the pro-apoptotic regulator Bim, driving mycolactone treated mammalian cells into apoptosis. The central role of Bim-dependent apoptosis in BU pathogenesis deduced from our experiments with cultured mammalian cells was further verified in an experimental M. ulcerans infection model. As predicted by the model, M. ulcerans infected Bim knockout mice did not develop necrotic BU lesions with large clusters of extracellular bacteria, but were able to contain the mycobacterial multiplication. Our findings provide a new coherent and comprehensive concept of BU pathogenesis.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bieri</LastName>
<ForeName>Raphael</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Swiss Tropical and Public Health Institute , Socinstrasse 57, 4002 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>University of Basel , Petersplatz 1, 4003 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Scherr</LastName>
<ForeName>Nicole</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Swiss Tropical and Public Health Institute , Socinstrasse 57, 4002 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>University of Basel , Petersplatz 1, 4003 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ruf</LastName>
<ForeName>Marie-Thérèse</ForeName>
<Initials>MT</Initials>
<AffiliationInfo><Affiliation>Swiss Tropical and Public Health Institute , Socinstrasse 57, 4002 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>University of Basel , Petersplatz 1, 4003 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dangy</LastName>
<ForeName>Jean-Pierre</ForeName>
<Initials>JP</Initials>
<Identifier Source="ORCID">0000-0001-7368-195X</Identifier>
<AffiliationInfo><Affiliation>Swiss Tropical and Public Health Institute , Socinstrasse 57, 4002 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>University of Basel , Petersplatz 1, 4003 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gersbach</LastName>
<ForeName>Philipp</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich , Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gehringer</LastName>
<ForeName>Matthias</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich , Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Altmann</LastName>
<ForeName>Karl-Heinz</ForeName>
<Initials>KH</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich , Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pluschke</LastName>
<ForeName>Gerd</ForeName>
<Initials>G</Initials>
<Identifier Source="ORCID">0000-0003-1957-2925</Identifier>
<AffiliationInfo><Affiliation>Swiss Tropical and Public Health Institute , Socinstrasse 57, 4002 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>University of Basel , Petersplatz 1, 4003 Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>03</Month>
<Day>27</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>ACS Chem Biol</MedlineTA>
<NlmUniqueID>101282906</NlmUniqueID>
<ISSNLinking>1554-8929</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000072224">Bcl-2-Like Protein 11</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D018942">Macrolides</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D046912">Multiprotein Complexes</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C117218">mycolactone</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="C546842">MTOR protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D000076225">Mechanistic Target of Rapamycin Complex 2</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017209" MajorTopicYN="Y">Apoptosis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000072224" MajorTopicYN="N">Bcl-2-Like Protein 11</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054312" MajorTopicYN="N">Buruli Ulcer</DescriptorName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055786" MajorTopicYN="N">Gene Knockout Techniques</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018942" MajorTopicYN="N">Macrolides</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
<QualifierName UI="Q000633" MajorTopicYN="N">toxicity</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000076225" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 2</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D046912" MajorTopicYN="N">Multiprotein Complexes</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019911" MajorTopicYN="N">Mycobacterium ulcerans</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2017</Year>
<Month>3</Month>
<Day>16</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2017</Year>
<Month>9</Month>
<Day>13</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2017</Year>
<Month>3</Month>
<Day>16</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">28294596</ArticleId>
<ArticleId IdType="doi">10.1021/acschembio.7b00053</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Suisse</li>
</country>
<region><li>Canton de Zurich</li>
</region>
<settlement><li>Zurich</li>
</settlement>
</list>
<tree><country name="Suisse"><noRegion><name sortKey="Bieri, Raphael" sort="Bieri, Raphael" uniqKey="Bieri R" first="Raphael" last="Bieri">Raphael Bieri</name>
</noRegion>
<name sortKey="Altmann, Karl Heinz" sort="Altmann, Karl Heinz" uniqKey="Altmann K" first="Karl-Heinz" last="Altmann">Karl-Heinz Altmann</name>
<name sortKey="Bieri, Raphael" sort="Bieri, Raphael" uniqKey="Bieri R" first="Raphael" last="Bieri">Raphael Bieri</name>
<name sortKey="Dangy, Jean Pierre" sort="Dangy, Jean Pierre" uniqKey="Dangy J" first="Jean-Pierre" last="Dangy">Jean-Pierre Dangy</name>
<name sortKey="Dangy, Jean Pierre" sort="Dangy, Jean Pierre" uniqKey="Dangy J" first="Jean-Pierre" last="Dangy">Jean-Pierre Dangy</name>
<name sortKey="Gehringer, Matthias" sort="Gehringer, Matthias" uniqKey="Gehringer M" first="Matthias" last="Gehringer">Matthias Gehringer</name>
<name sortKey="Gersbach, Philipp" sort="Gersbach, Philipp" uniqKey="Gersbach P" first="Philipp" last="Gersbach">Philipp Gersbach</name>
<name sortKey="Pluschke, Gerd" sort="Pluschke, Gerd" uniqKey="Pluschke G" first="Gerd" last="Pluschke">Gerd Pluschke</name>
<name sortKey="Pluschke, Gerd" sort="Pluschke, Gerd" uniqKey="Pluschke G" first="Gerd" last="Pluschke">Gerd Pluschke</name>
<name sortKey="Ruf, Marie Therese" sort="Ruf, Marie Therese" uniqKey="Ruf M" first="Marie-Thérèse" last="Ruf">Marie-Thérèse Ruf</name>
<name sortKey="Ruf, Marie Therese" sort="Ruf, Marie Therese" uniqKey="Ruf M" first="Marie-Thérèse" last="Ruf">Marie-Thérèse Ruf</name>
<name sortKey="Scherr, Nicole" sort="Scherr, Nicole" uniqKey="Scherr N" first="Nicole" last="Scherr">Nicole Scherr</name>
<name sortKey="Scherr, Nicole" sort="Scherr, Nicole" uniqKey="Scherr N" first="Nicole" last="Scherr">Nicole Scherr</name>
</country>
</tree>
</affiliations>
</record>

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	Serveur d'exploration sur la rapamycine et les champignons
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The Macrolide Toxin Mycolactone Promotes Bim-Dependent Apoptosis in Buruli Ulcer through Inhibition of mTOR.

The Macrolide Toxin Mycolactone Promotes Bim-Dependent Apoptosis in Buruli Ulcer through Inhibition of mTOR.

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