Secretion of FK506/FK520 and rapamycin by Streptomyces inhibits the growth of competing Saccharomyces cerevisiae and Cryptococcus neoformans.
Identifieur interne : 001A51 ( Main/Exploration ); précédent : 001A50; suivant : 001A52Secretion of FK506/FK520 and rapamycin by Streptomyces inhibits the growth of competing Saccharomyces cerevisiae and Cryptococcus neoformans.
Auteurs : Cristl Arndt ; Maria Cristina Cruz ; Maria E. Cardenas ; Joseph HeitmanSource :
- Microbiology (Reading, England) [ 1350-0872 ] ; 1999.
Descripteurs français
- KwdFr :
- Antibiose (MeSH), Calcineurine (métabolisme), Cryptococcus neoformans (croissance et développement), Cryptococcus neoformans (effets des médicaments et des substances chimiques), Immunosuppresseurs (métabolisme), Immunosuppresseurs (pharmacologie), Inhibiteurs de la calcineurine (MeSH), Phosphotransferases (métabolisme), Saccharomyces cerevisiae (croissance et développement), Saccharomyces cerevisiae (effets des médicaments et des substances chimiques), Sirolimus (métabolisme), Sirolimus (pharmacologie), Streptomyces (croissance et développement), Streptomyces (métabolisme), Tacrolimus (métabolisme), Tacrolimus (pharmacologie).
- MESH :
- croissance et développement : Cryptococcus neoformans, Saccharomyces cerevisiae, Streptomyces.
- effets des médicaments et des substances chimiques : Cryptococcus neoformans, Saccharomyces cerevisiae.
- métabolisme : Calcineurine, Immunosuppresseurs, Phosphotransferases, Sirolimus, Streptomyces, Tacrolimus.
- pharmacologie : Immunosuppresseurs, Sirolimus, Tacrolimus.
- Antibiose, Inhibiteurs de la calcineurine.
English descriptors
- KwdEn :
- Antibiosis (MeSH), Calcineurin (metabolism), Calcineurin Inhibitors (MeSH), Cryptococcus neoformans (drug effects), Cryptococcus neoformans (growth & development), Immunosuppressive Agents (metabolism), Immunosuppressive Agents (pharmacology), Phosphotransferases (metabolism), Saccharomyces cerevisiae (drug effects), Saccharomyces cerevisiae (growth & development), Sirolimus (metabolism), Sirolimus (pharmacology), Streptomyces (growth & development), Streptomyces (metabolism), Tacrolimus (metabolism), Tacrolimus (pharmacology).
- MESH :
- chemical , metabolism : Calcineurin, Immunosuppressive Agents, Phosphotransferases, Sirolimus, Tacrolimus.
- drug effects : Cryptococcus neoformans, Saccharomyces cerevisiae.
- growth & development : Cryptococcus neoformans, Saccharomyces cerevisiae, Streptomyces.
- metabolism : Streptomyces.
- chemical , pharmacology : Immunosuppressive Agents, Sirolimus, Tacrolimus.
- Antibiosis, Calcineurin Inhibitors.
Abstract
FK506 and rapamycin are immunosuppressants that inhibit signalling cascades required for T-cell activation, yet both are natural products of Streptomyces that live in the soil. FK506 and rapamycin also have potent antimicrobial activity against yeast and pathogenic fungi, suggesting a natural role in inhibiting growth of competing micro-organisms. The immunosuppressive and antimicrobial activities of FK506 and rapamycin are mediated by binding to the FKBP12 prolyl isomerase and the resulting FKBP12/FK506 and FKBP12/rapamycin complexes inhibit conserved protein targets, either the phosphatase calcineurin or the TOR (target of rapamycin) kinases, respectively. Streptomyces sp., 'Streptomyces hygroscopicus subsp. ascomyceticus' and Streptomyces hygroscopicus, which produce FK506, FK520 (also known as ascomycin, a C21 ethyl derivative of FK506) and rapamycin, respectively, produced toxins that inhibited the growth of competing cells of the yeast Saccharomyces cerevisiae and the pathogenic fungus Cryptococcus neoformans. Yeast and fungal mutants lacking FKBP12 or expressing dominant drug-resistant calcineurin or TOR mutants were resistant to FK506 and rapamycin, and to the toxins produced by Streptomyces. Streptomyces strains with mutations in the FK506 or rapamycin biosynthetic enzymes were impaired in toxin production. Finally, the toxins secreted by 'S. hygroscopicus subsp. ascomyceticus' and S. hygroscopicus promoted formation of FKBP12/calcineurin and FKBP12/TOR complexes in a two-hybrid assay and mutations that rendered calcineurin or TOR drug-resistant prevented interaction. These observations support the hypothesis that Streptomyces evolved to secrete FK506, FK520 and rapamycin as toxins to inhibit the growth of competing yeast and fungi.
DOI: 10.1099/13500872-145-8-1989
PubMed: 10463165
Affiliations:
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Cardenas</name></author><author><name sortKey="Heitman, Joseph" sort="Heitman, Joseph" uniqKey="Heitman J" first="Joseph" last="Heitman">Joseph Heitman</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1999">1999</date><idno type="RBID">pubmed:10463165</idno><idno type="pmid">10463165</idno><idno type="doi">10.1099/13500872-145-8-1989</idno><idno type="wicri:Area/Main/Corpus">001A54</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001A54</idno><idno type="wicri:Area/Main/Curation">001A54</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">001A54</idno><idno type="wicri:Area/Main/Exploration">001A54</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Secretion of FK506/FK520 and rapamycin by Streptomyces inhibits the growth of competing Saccharomyces cerevisiae and Cryptococcus neoformans.</title><author><name sortKey="Arndt, Cristl" sort="Arndt, Cristl" uniqKey="Arndt C" first="Cristl" last="Arndt">Cristl Arndt</name></author><author><name sortKey="Cruz, Maria Cristina" sort="Cruz, Maria Cristina" uniqKey="Cruz M" first="Maria Cristina" last="Cruz">Maria Cristina Cruz</name></author><author><name sortKey="Cardenas, Maria E" sort="Cardenas, Maria E" uniqKey="Cardenas M" first="Maria E" last="Cardenas">Maria E. Cardenas</name></author><author><name sortKey="Heitman, Joseph" sort="Heitman, Joseph" uniqKey="Heitman J" first="Joseph" last="Heitman">Joseph Heitman</name></author></analytic><series><title level="j">Microbiology (Reading, England)</title><idno type="ISSN">1350-0872</idno><imprint><date when="1999" type="published">1999</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibiosis (MeSH)</term><term>Calcineurin (metabolism)</term><term>Calcineurin Inhibitors (MeSH)</term><term>Cryptococcus neoformans (drug effects)</term><term>Cryptococcus neoformans (growth & development)</term><term>Immunosuppressive Agents (metabolism)</term><term>Immunosuppressive Agents (pharmacology)</term><term>Phosphotransferases (metabolism)</term><term>Saccharomyces cerevisiae (drug effects)</term><term>Saccharomyces cerevisiae (growth & development)</term><term>Sirolimus (metabolism)</term><term>Sirolimus (pharmacology)</term><term>Streptomyces (growth & development)</term><term>Streptomyces (metabolism)</term><term>Tacrolimus (metabolism)</term><term>Tacrolimus (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antibiose (MeSH)</term><term>Calcineurine (métabolisme)</term><term>Cryptococcus neoformans (croissance et développement)</term><term>Cryptococcus neoformans (effets des médicaments et des substances chimiques)</term><term>Immunosuppresseurs (métabolisme)</term><term>Immunosuppresseurs (pharmacologie)</term><term>Inhibiteurs de la calcineurine (MeSH)</term><term>Phosphotransferases (métabolisme)</term><term>Saccharomyces cerevisiae (croissance et développement)</term><term>Saccharomyces cerevisiae (effets des médicaments et des substances chimiques)</term><term>Sirolimus (métabolisme)</term><term>Sirolimus (pharmacologie)</term><term>Streptomyces (croissance et développement)</term><term>Streptomyces (métabolisme)</term><term>Tacrolimus (métabolisme)</term><term>Tacrolimus (pharmacologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcineurin</term><term>Immunosuppressive Agents</term><term>Phosphotransferases</term><term>Sirolimus</term><term>Tacrolimus</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Cryptococcus neoformans</term><term>Saccharomyces cerevisiae</term><term>Streptomyces</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cryptococcus neoformans</term><term>Saccharomyces cerevisiae</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Cryptococcus neoformans</term><term>Saccharomyces cerevisiae</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Cryptococcus neoformans</term><term>Saccharomyces cerevisiae</term><term>Streptomyces</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Streptomyces</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Calcineurine</term><term>Immunosuppresseurs</term><term>Phosphotransferases</term><term>Sirolimus</term><term>Streptomyces</term><term>Tacrolimus</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Immunosuppresseurs</term><term>Sirolimus</term><term>Tacrolimus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Immunosuppressive Agents</term><term>Sirolimus</term><term>Tacrolimus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Antibiosis</term><term>Calcineurin Inhibitors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Antibiose</term><term>Inhibiteurs de la calcineurine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">FK506 and rapamycin are immunosuppressants that inhibit signalling cascades required for T-cell activation, yet both are natural products of Streptomyces that live in the soil. FK506 and rapamycin also have potent antimicrobial activity against yeast and pathogenic fungi, suggesting a natural role in inhibiting growth of competing micro-organisms. The immunosuppressive and antimicrobial activities of FK506 and rapamycin are mediated by binding to the FKBP12 prolyl isomerase and the resulting FKBP12/FK506 and FKBP12/rapamycin complexes inhibit conserved protein targets, either the phosphatase calcineurin or the TOR (target of rapamycin) kinases, respectively. Streptomyces sp., 'Streptomyces hygroscopicus subsp. ascomyceticus' and Streptomyces hygroscopicus, which produce FK506, FK520 (also known as ascomycin, a C21 ethyl derivative of FK506) and rapamycin, respectively, produced toxins that inhibited the growth of competing cells of the yeast Saccharomyces cerevisiae and the pathogenic fungus Cryptococcus neoformans. Yeast and fungal mutants lacking FKBP12 or expressing dominant drug-resistant calcineurin or TOR mutants were resistant to FK506 and rapamycin, and to the toxins produced by Streptomyces. Streptomyces strains with mutations in the FK506 or rapamycin biosynthetic enzymes were impaired in toxin production. Finally, the toxins secreted by 'S. hygroscopicus subsp. ascomyceticus' and S. hygroscopicus promoted formation of FKBP12/calcineurin and FKBP12/TOR complexes in a two-hybrid assay and mutations that rendered calcineurin or TOR drug-resistant prevented interaction. These observations support the hypothesis that Streptomyces evolved to secrete FK506, FK520 and rapamycin as toxins to inhibit the growth of competing yeast and fungi.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">10463165</PMID><DateCompleted><Year>1999</Year><Month>11</Month><Day>08</Day></DateCompleted><DateRevised><Year>2020</Year><Month>08</Month><Day>26</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1350-0872</ISSN><JournalIssue CitedMedium="Print"><Volume>145 ( Pt 8)</Volume><PubDate><Year>1999</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Microbiology (Reading, England)</Title><ISOAbbreviation>Microbiology (Reading)</ISOAbbreviation></Journal><ArticleTitle>Secretion of FK506/FK520 and rapamycin by Streptomyces inhibits the growth of competing Saccharomyces cerevisiae and Cryptococcus neoformans.</ArticleTitle><Pagination><MedlinePgn>1989-2000</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1099/13500872-145-8-1989</ELocationID><Abstract><AbstractText>FK506 and rapamycin are immunosuppressants that inhibit signalling cascades required for T-cell activation, yet both are natural products of Streptomyces that live in the soil. FK506 and rapamycin also have potent antimicrobial activity against yeast and pathogenic fungi, suggesting a natural role in inhibiting growth of competing micro-organisms. The immunosuppressive and antimicrobial activities of FK506 and rapamycin are mediated by binding to the FKBP12 prolyl isomerase and the resulting FKBP12/FK506 and FKBP12/rapamycin complexes inhibit conserved protein targets, either the phosphatase calcineurin or the TOR (target of rapamycin) kinases, respectively. Streptomyces sp., 'Streptomyces hygroscopicus subsp. ascomyceticus' and Streptomyces hygroscopicus, which produce FK506, FK520 (also known as ascomycin, a C21 ethyl derivative of FK506) and rapamycin, respectively, produced toxins that inhibited the growth of competing cells of the yeast Saccharomyces cerevisiae and the pathogenic fungus Cryptococcus neoformans. Yeast and fungal mutants lacking FKBP12 or expressing dominant drug-resistant calcineurin or TOR mutants were resistant to FK506 and rapamycin, and to the toxins produced by Streptomyces. Streptomyces strains with mutations in the FK506 or rapamycin biosynthetic enzymes were impaired in toxin production. Finally, the toxins secreted by 'S. hygroscopicus subsp. ascomyceticus' and S. hygroscopicus promoted formation of FKBP12/calcineurin and FKBP12/TOR complexes in a two-hybrid assay and mutations that rendered calcineurin or TOR drug-resistant prevented interaction. These observations support the hypothesis that Streptomyces evolved to secrete FK506, FK520 and rapamycin as toxins to inhibit the growth of competing yeast and fungi.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Arndt</LastName><ForeName>Cristl</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Cruz</LastName><ForeName>Maria Cristina</ForeName><Initials>MC</Initials></Author><Author ValidYN="Y"><LastName>Cardenas</LastName><ForeName>Maria E</ForeName><Initials>ME</Initials></Author><Author ValidYN="Y"><LastName>Heitman</LastName><ForeName>Joseph</ForeName><Initials>J</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="N"><Grant><GrantID>AI41937</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>CA77075</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI39115</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Microbiology (Reading)</MedlineTA><NlmUniqueID>9430468</NlmUniqueID><ISSNLinking>1350-0872</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D065095">Calcineurin Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007166">Immunosuppressive Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.-</RegistryNumber><NameOfSubstance UI="D010770">Phosphotransferases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.3.16</RegistryNumber><NameOfSubstance UI="D019703">Calcineurin</NameOfSubstance></Chemical><Chemical><RegistryNumber>W36ZG6FT64</RegistryNumber><NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance></Chemical><Chemical><RegistryNumber>WM0HAQ4WNM</RegistryNumber><NameOfSubstance UI="D016559">Tacrolimus</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000898" MajorTopicYN="N">Antibiosis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019703" MajorTopicYN="N">Calcineurin</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D065095" MajorTopicYN="N">Calcineurin Inhibitors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003455" MajorTopicYN="N">Cryptococcus neoformans</DescriptorName><QualifierName 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MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013302" MajorTopicYN="N">Streptomyces</DescriptorName><QualifierName UI="Q000254" MajorTopicYN="N">growth & development</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016559" MajorTopicYN="N">Tacrolimus</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1999</Year><Month>8</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1999</Year><Month>8</Month><Day>27</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1999</Year><Month>8</Month><Day>27</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10463165</ArticleId><ArticleId IdType="doi">10.1099/13500872-145-8-1989</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list></list><tree><noCountry><name sortKey="Arndt, Cristl" sort="Arndt, Cristl" uniqKey="Arndt C" first="Cristl" last="Arndt">Cristl Arndt</name><name sortKey="Cardenas, Maria E" sort="Cardenas, Maria E" uniqKey="Cardenas M" first="Maria E" last="Cardenas">Maria E. Cardenas</name><name sortKey="Cruz, Maria Cristina" sort="Cruz, Maria Cristina" uniqKey="Cruz M" first="Maria Cristina" last="Cruz">Maria Cristina Cruz</name><name sortKey="Heitman, Joseph" sort="Heitman, Joseph" uniqKey="Heitman J" first="Joseph" last="Heitman">Joseph Heitman</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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