The Transcription Factor Stp2 Is Important for Candida albicans Biofilm Establishment and Sustainability.
Identifieur interne : 000029 ( Main/Exploration ); précédent : 000028; suivant : 000030The Transcription Factor Stp2 Is Important for Candida albicans Biofilm Establishment and Sustainability.
Auteurs : Bettina Böttcher [Allemagne] ; Bianca Hoffmann [Allemagne] ; Enrico Garbe [Allemagne] ; Tobias Weise [Allemagne] ; Zoltán Cseresnyés [Allemagne] ; Philipp Brandt [Allemagne] ; Stefanie Dietrich [Allemagne] ; Dominik Driesch [Allemagne] ; Marc Thilo Figge [Allemagne] ; Slavena Vylkova [Allemagne]Source :
- Frontiers in microbiology [ 1664-302X ] ; 2020.
Abstract
The fungal pathogen Candida albicans forms polymorphic biofilms where hyphal morphogenesis and metabolic adaptation are tightly coordinated by a complex intertwined network of transcription factors. The sensing and metabolism of amino acids play important roles during various phases of biofilm development - from adhesion to maturation. Stp2 is a transcription factor that activates the expression of amino acid permease genes and is required for environmental alkalinization and hyphal growth in vitro and during macrophage phagocytosis. While it is well established that Stp2 is activated in response to external amino acids, its role in biofilm formation remains unknown. In addition to widely used techniques, we applied newly developed approaches for automated image analysis to quantify Stp2-regulated filamentation and biofilm growth. Our results show that in the stp2Δ deletion mutant adherence to abiotic surfaces and initial germ tube formation were strongly impaired, but formed mature biofilms with cell density and morphological structures comparable to the control strains. Stp2-dependent nutrient adaptation appeared to play an important role in biofilm development: stp2Δ biofilms formed under continuous nutrient flow displayed an overall reduction in biofilm formation, whereas under steady conditions the mutant strain formed biofilms with lower metabolic activity, resulting in increased cell survival and biofilm longevity. A deletion of STP2 led to increased rapamycin susceptibility and transcriptional activation of GCN4, the transcriptional regulator of the general amino acid control pathway, demonstrating a connection of Stp2 to other nutrient-responsive pathways. In summary, the transcription factor Stp2 is important for C. albicans biofilm formation, where it contributes to adherence and induction of morphogenesis, and mediates nutrient adaption and cell longevity in mature biofilms.
DOI: 10.3389/fmicb.2020.00794
PubMed: 32425915
PubMed Central: PMC7203782
Affiliations:
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Hans Knöll Institute, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32425915</idno><idno type="pmid">32425915</idno><idno type="doi">10.3389/fmicb.2020.00794</idno><idno type="pmc">PMC7203782</idno><idno type="wicri:Area/Main/Corpus">000072</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000072</idno><idno type="wicri:Area/Main/Curation">000072</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000072</idno><idno type="wicri:Area/Main/Exploration">000072</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The Transcription Factor Stp2 Is Important for <i>Candida albicans</i> Biofilm Establishment and Sustainability.</title><author><name sortKey="Bottcher, Bettina" sort="Bottcher, Bettina" uniqKey="Bottcher B" first="Bettina" last="Böttcher">Bettina Böttcher</name><affiliation wicri:level="1"><nlm:affiliation>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Hoffmann, Bianca" sort="Hoffmann, Bianca" uniqKey="Hoffmann B" first="Bianca" last="Hoffmann">Bianca Hoffmann</name><affiliation wicri:level="1"><nlm:affiliation>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Garbe, Enrico" sort="Garbe, Enrico" uniqKey="Garbe E" first="Enrico" last="Garbe">Enrico Garbe</name><affiliation wicri:level="1"><nlm:affiliation>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Weise, Tobias" sort="Weise, Tobias" uniqKey="Weise T" first="Tobias" last="Weise">Tobias Weise</name><affiliation wicri:level="1"><nlm:affiliation>BioControl Jena, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>BioControl Jena, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Cseresnyes, Zoltan" sort="Cseresnyes, Zoltan" uniqKey="Cseresnyes Z" first="Zoltán" last="Cseresnyés">Zoltán Cseresnyés</name><affiliation wicri:level="1"><nlm:affiliation>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Brandt, Philipp" sort="Brandt, Philipp" uniqKey="Brandt P" first="Philipp" last="Brandt">Philipp Brandt</name><affiliation wicri:level="1"><nlm:affiliation>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Dietrich, Stefanie" sort="Dietrich, Stefanie" uniqKey="Dietrich S" first="Stefanie" last="Dietrich">Stefanie Dietrich</name><affiliation wicri:level="1"><nlm:affiliation>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Driesch, Dominik" sort="Driesch, Dominik" uniqKey="Driesch D" first="Dominik" last="Driesch">Dominik Driesch</name><affiliation wicri:level="1"><nlm:affiliation>BioControl Jena, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>BioControl Jena, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Figge, Marc Thilo" sort="Figge, Marc Thilo" uniqKey="Figge M" first="Marc Thilo" last="Figge">Marc Thilo Figge</name><affiliation wicri:level="1"><nlm:affiliation>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University Jena</wicri:regionArea><wicri:noRegion>Friedrich Schiller University Jena</wicri:noRegion><wicri:noRegion>Friedrich Schiller University Jena</wicri:noRegion><wicri:noRegion>Friedrich Schiller University Jena</wicri:noRegion></affiliation></author><author><name sortKey="Vylkova, Slavena" sort="Vylkova, Slavena" uniqKey="Vylkova S" first="Slavena" last="Vylkova">Slavena Vylkova</name><affiliation wicri:level="1"><nlm:affiliation>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author></analytic><series><title level="j">Frontiers in microbiology</title><idno type="ISSN">1664-302X</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The fungal pathogen <i>Candida albicans</i> forms polymorphic biofilms where hyphal morphogenesis and metabolic adaptation are tightly coordinated by a complex intertwined network of transcription factors. The sensing and metabolism of amino acids play important roles during various phases of biofilm development - from adhesion to maturation. Stp2 is a transcription factor that activates the expression of amino acid permease genes and is required for environmental alkalinization and hyphal growth <i>in vitro</i> and during macrophage phagocytosis. While it is well established that Stp2 is activated in response to external amino acids, its role in biofilm formation remains unknown. In addition to widely used techniques, we applied newly developed approaches for automated image analysis to quantify Stp2-regulated filamentation and biofilm growth. Our results show that in the <i>stp2</i>Δ deletion mutant adherence to abiotic surfaces and initial germ tube formation were strongly impaired, but formed mature biofilms with cell density and morphological structures comparable to the control strains. Stp2-dependent nutrient adaptation appeared to play an important role in biofilm development: <i>stp2</i>Δ biofilms formed under continuous nutrient flow displayed an overall reduction in biofilm formation, whereas under steady conditions the mutant strain formed biofilms with lower metabolic activity, resulting in increased cell survival and biofilm longevity. A deletion of <i>STP2</i> led to increased rapamycin susceptibility and transcriptional activation of <i>GCN4</i>, the transcriptional regulator of the general amino acid control pathway, demonstrating a connection of Stp2 to other nutrient-responsive pathways. In summary, the transcription factor Stp2 is important for <i>C. albicans</i> biofilm formation, where it contributes to adherence and induction of morphogenesis, and mediates nutrient adaption and cell longevity in mature biofilms.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32425915</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>28</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1664-302X</ISSN><JournalIssue CitedMedium="Print"><Volume>11</Volume><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>Frontiers in microbiology</Title><ISOAbbreviation>Front Microbiol</ISOAbbreviation></Journal><ArticleTitle>The Transcription Factor Stp2 Is Important for <i>Candida albicans</i> Biofilm Establishment and Sustainability.</ArticleTitle><Pagination><MedlinePgn>794</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fmicb.2020.00794</ELocationID><Abstract><AbstractText>The fungal pathogen <i>Candida albicans</i> forms polymorphic biofilms where hyphal morphogenesis and metabolic adaptation are tightly coordinated by a complex intertwined network of transcription factors. The sensing and metabolism of amino acids play important roles during various phases of biofilm development - from adhesion to maturation. Stp2 is a transcription factor that activates the expression of amino acid permease genes and is required for environmental alkalinization and hyphal growth <i>in vitro</i> and during macrophage phagocytosis. While it is well established that Stp2 is activated in response to external amino acids, its role in biofilm formation remains unknown. In addition to widely used techniques, we applied newly developed approaches for automated image analysis to quantify Stp2-regulated filamentation and biofilm growth. Our results show that in the <i>stp2</i>Δ deletion mutant adherence to abiotic surfaces and initial germ tube formation were strongly impaired, but formed mature biofilms with cell density and morphological structures comparable to the control strains. Stp2-dependent nutrient adaptation appeared to play an important role in biofilm development: <i>stp2</i>Δ biofilms formed under continuous nutrient flow displayed an overall reduction in biofilm formation, whereas under steady conditions the mutant strain formed biofilms with lower metabolic activity, resulting in increased cell survival and biofilm longevity. A deletion of <i>STP2</i> led to increased rapamycin susceptibility and transcriptional activation of <i>GCN4</i>, the transcriptional regulator of the general amino acid control pathway, demonstrating a connection of Stp2 to other nutrient-responsive pathways. In summary, the transcription factor Stp2 is important for <i>C. albicans</i> biofilm formation, where it contributes to adherence and induction of morphogenesis, and mediates nutrient adaption and cell longevity in mature biofilms.</AbstractText><CopyrightInformation>Copyright © 2020 Böttcher, Hoffmann, Garbe, Weise, Cseresnyés, Brandt, Dietrich, Driesch, Figge and Vylkova.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Böttcher</LastName><ForeName>Bettina</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hoffmann</LastName><ForeName>Bianca</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Garbe</LastName><ForeName>Enrico</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weise</LastName><ForeName>Tobias</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>BioControl Jena, Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cseresnyés</LastName><ForeName>Zoltán</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brandt</LastName><ForeName>Philipp</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dietrich</LastName><ForeName>Stefanie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Driesch</LastName><ForeName>Dominik</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>BioControl Jena, Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Figge</LastName><ForeName>Marc Thilo</ForeName><Initials>MT</Initials><AffiliationInfo><Affiliation>Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vylkova</LastName><ForeName>Slavena</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>04</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Microbiol</MedlineTA><NlmUniqueID>101548977</NlmUniqueID><ISSNLinking>1664-302X</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Biofilms</Keyword><Keyword MajorTopicYN="N">Candida albicans</Keyword><Keyword MajorTopicYN="N">Stp2</Keyword><Keyword MajorTopicYN="N">amino acids</Keyword><Keyword MajorTopicYN="N">automated image analysis</Keyword><Keyword MajorTopicYN="N">filamentation</Keyword><Keyword MajorTopicYN="N">metabolism</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>02</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>04</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>5</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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