The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence
Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recr...
Gespeichert in:
| Veröffentlicht in: | PLoS pathogens 2020-07, Vol.16 (7), p.e1008645 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 7 |
| container_start_page | e1008645 |
| container_title | PLoS pathogens |
| container_volume | 16 |
| creator | Ries, Laure N A Pardeshi, Lakhansing Dong, Zhiqiang Tan, Kaeling Steenwyk, Jacob L Colabardini, Ana Cristina Ferreira Filho, Jaire A de Castro, Patricia A Silva, Lilian P Preite, Nycolas W Almeida, Fausto de Assis, Leandro J Dos Santos, Renato A C Bowyer, Paul Bromley, Michael Owens, Rebecca A Doyle, Sean Demasi, Marilene Hernández, Diego C R Netto, Luís Eduardo S Pupo, Monica T Rokas, Antonis Loures, Flavio V Wong, Koon H Goldman, Gustavo H |
| description | Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species. |
| doi_str_mv | 10.1371/journal.ppat.1008645 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2434497378</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A631237490</galeid><doaj_id>oai_doaj_org_article_a8f50cb4322d4e79bd71b302c6284ecd</doaj_id><sourcerecordid>A631237490</sourcerecordid><originalsourceid>FETCH-LOGICAL-c661t-fca890a9f9c8f4e8f72124265bdc54e29c81c0f8eab37118c4cdb371a5ede8033</originalsourceid><addsrcrecordid>eNqVkktv1DAUhSMEoqXwDxBEYgMSM_iV1wZpVPEYqQKpDGvLca4zrjx2ajtVu-G343TSqoO6QVnk6uS7x74nN8teY7TEtMKfLtzorTDLYRBxiRGqS1Y8yY5xUdBFRSv29EF9lL0I4QIhhikun2dHlJRl1ZToOPuz2UK-CgP4XhszhlyNO92LmKrohQ3S6yFqZ3MlZHQ-P-_NJtch17vB-ShszFVSe6NddNfa5q124cbGLYQECdvlAYxaDN5FkJPPx1vxSvvRgJXwMnumhAnwan6fZL-_ftmcfl-c_fy2Pl2dLWRZ4rhQUtQNEo1qZK0Y1KoimDBSFm0nCwYkyVgiVYNoUzS4lkx2UyUK6KBGlJ5kb_e-g3GBz9EFThhlrEkJ1YlY74nOiQs-eL0T_oY7ofmt4HzPhY9aGuCiVgWSLaOEdAyqpu0q3FJEZElqBrJLXp_n08Z2B50Em7I0B6aHX6ze8t5d8YrWLP2YZPB-NvDucoQQ-U4HCcYIC26c7k0YY7TEJKHv_kEfn26mepEG0Fa5dK6cTPmqpMmmYg1K1PIRKj0d7LR0FpRO-kHDh4OGxES4jr0YQ-DrX-f_wf44ZNmeld6F4EHdZ4cRn7b_bkg-bT-ftz-1vXmY-33T3brTv_RaA3Y</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2434497378</pqid></control><display><type>article</type><title>The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>PubMed Central</source><creator>Ries, Laure N A ; Pardeshi, Lakhansing ; Dong, Zhiqiang ; Tan, Kaeling ; Steenwyk, Jacob L ; Colabardini, Ana Cristina ; Ferreira Filho, Jaire A ; de Castro, Patricia A ; Silva, Lilian P ; Preite, Nycolas W ; Almeida, Fausto ; de Assis, Leandro J ; Dos Santos, Renato A C ; Bowyer, Paul ; Bromley, Michael ; Owens, Rebecca A ; Doyle, Sean ; Demasi, Marilene ; Hernández, Diego C R ; Netto, Luís Eduardo S ; Pupo, Monica T ; Rokas, Antonis ; Loures, Flavio V ; Wong, Koon H ; Goldman, Gustavo H</creator><contributor>Cramer, Robert A.</contributor><creatorcontrib>Ries, Laure N A ; Pardeshi, Lakhansing ; Dong, Zhiqiang ; Tan, Kaeling ; Steenwyk, Jacob L ; Colabardini, Ana Cristina ; Ferreira Filho, Jaire A ; de Castro, Patricia A ; Silva, Lilian P ; Preite, Nycolas W ; Almeida, Fausto ; de Assis, Leandro J ; Dos Santos, Renato A C ; Bowyer, Paul ; Bromley, Michael ; Owens, Rebecca A ; Doyle, Sean ; Demasi, Marilene ; Hernández, Diego C R ; Netto, Luís Eduardo S ; Pupo, Monica T ; Rokas, Antonis ; Loures, Flavio V ; Wong, Koon H ; Goldman, Gustavo H ; Cramer, Robert A.</creatorcontrib><description>Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1008645</identifier><identifier>PMID: 32667960</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animals ; Aspergillosis ; Aspergillosis - metabolism ; Aspergillosis - microbiology ; Aspergillus ; Aspergillus fumigatus ; Aspergillus fumigatus - metabolism ; Aspergillus fumigatus - pathogenicity ; Bioinformatics ; Biology ; Biology and Life Sciences ; Biosynthesis ; Clusters ; Cytokines ; Defects ; Enzymes ; Fungal infections ; Fungal Proteins - metabolism ; Fungi ; Gene expression ; Gene Expression Regulation, Fungal - physiology ; Genes ; Genetic aspects ; Genomics ; Gliotoxin ; Gliotoxin - biosynthesis ; Granulocytes ; Health aspects ; Health sciences ; Homology ; Immune response ; Immune system ; Immunomodulation ; Kinases ; Medicine ; Medicine and Health Sciences ; Metabolites ; Mice ; Model testing ; Neutrophils ; Opportunist infection ; Oxidation resistance ; Oxidative stress ; Oxidative Stress - physiology ; Oxidoreductase ; Pathogens ; Pharmaceutical sciences ; Phylogeny ; Secondary metabolites ; Transcription factors ; Transcription Factors - metabolism ; Virulence ; Virulence - physiology</subject><ispartof>PLoS pathogens, 2020-07, Vol.16 (7), p.e1008645</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Ries et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Ries et al 2020 Ries et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c661t-fca890a9f9c8f4e8f72124265bdc54e29c81c0f8eab37118c4cdb371a5ede8033</citedby><cites>FETCH-LOGICAL-c661t-fca890a9f9c8f4e8f72124265bdc54e29c81c0f8eab37118c4cdb371a5ede8033</cites><orcidid>0000-0002-7611-0201 ; 0000-0002-7248-6551 ; 0000-0002-9264-5118 ; 0000-0002-1125-2399 ; 0000-0002-2986-350X ; 0000-0003-0702-5465 ; 0000-0001-6545-1978 ; 0000-0002-4250-9177 ; 0000-0001-9996-0105 ; 0000-0001-9782-437X ; 0000-0002-3782-3698 ; 0000-0002-8436-595X ; 0000-0002-0143-6557</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384679/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384679/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32667960$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cramer, Robert A.</contributor><creatorcontrib>Ries, Laure N A</creatorcontrib><creatorcontrib>Pardeshi, Lakhansing</creatorcontrib><creatorcontrib>Dong, Zhiqiang</creatorcontrib><creatorcontrib>Tan, Kaeling</creatorcontrib><creatorcontrib>Steenwyk, Jacob L</creatorcontrib><creatorcontrib>Colabardini, Ana Cristina</creatorcontrib><creatorcontrib>Ferreira Filho, Jaire A</creatorcontrib><creatorcontrib>de Castro, Patricia A</creatorcontrib><creatorcontrib>Silva, Lilian P</creatorcontrib><creatorcontrib>Preite, Nycolas W</creatorcontrib><creatorcontrib>Almeida, Fausto</creatorcontrib><creatorcontrib>de Assis, Leandro J</creatorcontrib><creatorcontrib>Dos Santos, Renato A C</creatorcontrib><creatorcontrib>Bowyer, Paul</creatorcontrib><creatorcontrib>Bromley, Michael</creatorcontrib><creatorcontrib>Owens, Rebecca A</creatorcontrib><creatorcontrib>Doyle, Sean</creatorcontrib><creatorcontrib>Demasi, Marilene</creatorcontrib><creatorcontrib>Hernández, Diego C R</creatorcontrib><creatorcontrib>Netto, Luís Eduardo S</creatorcontrib><creatorcontrib>Pupo, Monica T</creatorcontrib><creatorcontrib>Rokas, Antonis</creatorcontrib><creatorcontrib>Loures, Flavio V</creatorcontrib><creatorcontrib>Wong, Koon H</creatorcontrib><creatorcontrib>Goldman, Gustavo H</creatorcontrib><title>The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.</description><subject>Animal models</subject><subject>Animals</subject><subject>Aspergillosis</subject><subject>Aspergillosis - metabolism</subject><subject>Aspergillosis - microbiology</subject><subject>Aspergillus</subject><subject>Aspergillus fumigatus</subject><subject>Aspergillus fumigatus - metabolism</subject><subject>Aspergillus fumigatus - pathogenicity</subject><subject>Bioinformatics</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Biosynthesis</subject><subject>Clusters</subject><subject>Cytokines</subject><subject>Defects</subject><subject>Enzymes</subject><subject>Fungal infections</subject><subject>Fungal Proteins - metabolism</subject><subject>Fungi</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Fungal - physiology</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomics</subject><subject>Gliotoxin</subject><subject>Gliotoxin - biosynthesis</subject><subject>Granulocytes</subject><subject>Health aspects</subject><subject>Health sciences</subject><subject>Homology</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunomodulation</subject><subject>Kinases</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolites</subject><subject>Mice</subject><subject>Model testing</subject><subject>Neutrophils</subject><subject>Opportunist infection</subject><subject>Oxidation resistance</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - physiology</subject><subject>Oxidoreductase</subject><subject>Pathogens</subject><subject>Pharmaceutical sciences</subject><subject>Phylogeny</subject><subject>Secondary metabolites</subject><subject>Transcription factors</subject><subject>Transcription Factors - metabolism</subject><subject>Virulence</subject><subject>Virulence - physiology</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVkktv1DAUhSMEoqXwDxBEYgMSM_iV1wZpVPEYqQKpDGvLca4zrjx2ajtVu-G343TSqoO6QVnk6uS7x74nN8teY7TEtMKfLtzorTDLYRBxiRGqS1Y8yY5xUdBFRSv29EF9lL0I4QIhhikun2dHlJRl1ZToOPuz2UK-CgP4XhszhlyNO92LmKrohQ3S6yFqZ3MlZHQ-P-_NJtch17vB-ShszFVSe6NddNfa5q124cbGLYQECdvlAYxaDN5FkJPPx1vxSvvRgJXwMnumhAnwan6fZL-_ftmcfl-c_fy2Pl2dLWRZ4rhQUtQNEo1qZK0Y1KoimDBSFm0nCwYkyVgiVYNoUzS4lkx2UyUK6KBGlJ5kb_e-g3GBz9EFThhlrEkJ1YlY74nOiQs-eL0T_oY7ofmt4HzPhY9aGuCiVgWSLaOEdAyqpu0q3FJEZElqBrJLXp_n08Z2B50Em7I0B6aHX6ze8t5d8YrWLP2YZPB-NvDucoQQ-U4HCcYIC26c7k0YY7TEJKHv_kEfn26mepEG0Fa5dK6cTPmqpMmmYg1K1PIRKj0d7LR0FpRO-kHDh4OGxES4jr0YQ-DrX-f_wf44ZNmeld6F4EHdZ4cRn7b_bkg-bT-ftz-1vXmY-33T3brTv_RaA3Y</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Ries, Laure N A</creator><creator>Pardeshi, Lakhansing</creator><creator>Dong, Zhiqiang</creator><creator>Tan, Kaeling</creator><creator>Steenwyk, Jacob L</creator><creator>Colabardini, Ana Cristina</creator><creator>Ferreira Filho, Jaire A</creator><creator>de Castro, Patricia A</creator><creator>Silva, Lilian P</creator><creator>Preite, Nycolas W</creator><creator>Almeida, Fausto</creator><creator>de Assis, Leandro J</creator><creator>Dos Santos, Renato A C</creator><creator>Bowyer, Paul</creator><creator>Bromley, Michael</creator><creator>Owens, Rebecca A</creator><creator>Doyle, Sean</creator><creator>Demasi, Marilene</creator><creator>Hernández, Diego C R</creator><creator>Netto, Luís Eduardo S</creator><creator>Pupo, Monica T</creator><creator>Rokas, Antonis</creator><creator>Loures, Flavio V</creator><creator>Wong, Koon H</creator><creator>Goldman, Gustavo H</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7611-0201</orcidid><orcidid>https://orcid.org/0000-0002-7248-6551</orcidid><orcidid>https://orcid.org/0000-0002-9264-5118</orcidid><orcidid>https://orcid.org/0000-0002-1125-2399</orcidid><orcidid>https://orcid.org/0000-0002-2986-350X</orcidid><orcidid>https://orcid.org/0000-0003-0702-5465</orcidid><orcidid>https://orcid.org/0000-0001-6545-1978</orcidid><orcidid>https://orcid.org/0000-0002-4250-9177</orcidid><orcidid>https://orcid.org/0000-0001-9996-0105</orcidid><orcidid>https://orcid.org/0000-0001-9782-437X</orcidid><orcidid>https://orcid.org/0000-0002-3782-3698</orcidid><orcidid>https://orcid.org/0000-0002-8436-595X</orcidid><orcidid>https://orcid.org/0000-0002-0143-6557</orcidid></search><sort><creationdate>20200701</creationdate><title>The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence</title><author>Ries, Laure N A ; Pardeshi, Lakhansing ; Dong, Zhiqiang ; Tan, Kaeling ; Steenwyk, Jacob L ; Colabardini, Ana Cristina ; Ferreira Filho, Jaire A ; de Castro, Patricia A ; Silva, Lilian P ; Preite, Nycolas W ; Almeida, Fausto ; de Assis, Leandro J ; Dos Santos, Renato A C ; Bowyer, Paul ; Bromley, Michael ; Owens, Rebecca A ; Doyle, Sean ; Demasi, Marilene ; Hernández, Diego C R ; Netto, Luís Eduardo S ; Pupo, Monica T ; Rokas, Antonis ; Loures, Flavio V ; Wong, Koon H ; Goldman, Gustavo H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c661t-fca890a9f9c8f4e8f72124265bdc54e29c81c0f8eab37118c4cdb371a5ede8033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Aspergillosis</topic><topic>Aspergillosis - metabolism</topic><topic>Aspergillosis - microbiology</topic><topic>Aspergillus</topic><topic>Aspergillus fumigatus</topic><topic>Aspergillus fumigatus - metabolism</topic><topic>Aspergillus fumigatus - pathogenicity</topic><topic>Bioinformatics</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Biosynthesis</topic><topic>Clusters</topic><topic>Cytokines</topic><topic>Defects</topic><topic>Enzymes</topic><topic>Fungal infections</topic><topic>Fungal Proteins - metabolism</topic><topic>Fungi</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Fungal - physiology</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomics</topic><topic>Gliotoxin</topic><topic>Gliotoxin - biosynthesis</topic><topic>Granulocytes</topic><topic>Health aspects</topic><topic>Health sciences</topic><topic>Homology</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunomodulation</topic><topic>Kinases</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metabolites</topic><topic>Mice</topic><topic>Model testing</topic><topic>Neutrophils</topic><topic>Opportunist infection</topic><topic>Oxidation resistance</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - physiology</topic><topic>Oxidoreductase</topic><topic>Pathogens</topic><topic>Pharmaceutical sciences</topic><topic>Phylogeny</topic><topic>Secondary metabolites</topic><topic>Transcription factors</topic><topic>Transcription Factors - metabolism</topic><topic>Virulence</topic><topic>Virulence - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ries, Laure N A</creatorcontrib><creatorcontrib>Pardeshi, Lakhansing</creatorcontrib><creatorcontrib>Dong, Zhiqiang</creatorcontrib><creatorcontrib>Tan, Kaeling</creatorcontrib><creatorcontrib>Steenwyk, Jacob L</creatorcontrib><creatorcontrib>Colabardini, Ana Cristina</creatorcontrib><creatorcontrib>Ferreira Filho, Jaire A</creatorcontrib><creatorcontrib>de Castro, Patricia A</creatorcontrib><creatorcontrib>Silva, Lilian P</creatorcontrib><creatorcontrib>Preite, Nycolas W</creatorcontrib><creatorcontrib>Almeida, Fausto</creatorcontrib><creatorcontrib>de Assis, Leandro J</creatorcontrib><creatorcontrib>Dos Santos, Renato A C</creatorcontrib><creatorcontrib>Bowyer, Paul</creatorcontrib><creatorcontrib>Bromley, Michael</creatorcontrib><creatorcontrib>Owens, Rebecca A</creatorcontrib><creatorcontrib>Doyle, Sean</creatorcontrib><creatorcontrib>Demasi, Marilene</creatorcontrib><creatorcontrib>Hernández, Diego C R</creatorcontrib><creatorcontrib>Netto, Luís Eduardo S</creatorcontrib><creatorcontrib>Pupo, Monica T</creatorcontrib><creatorcontrib>Rokas, Antonis</creatorcontrib><creatorcontrib>Loures, Flavio V</creatorcontrib><creatorcontrib>Wong, Koon H</creatorcontrib><creatorcontrib>Goldman, Gustavo H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ries, Laure N A</au><au>Pardeshi, Lakhansing</au><au>Dong, Zhiqiang</au><au>Tan, Kaeling</au><au>Steenwyk, Jacob L</au><au>Colabardini, Ana Cristina</au><au>Ferreira Filho, Jaire A</au><au>de Castro, Patricia A</au><au>Silva, Lilian P</au><au>Preite, Nycolas W</au><au>Almeida, Fausto</au><au>de Assis, Leandro J</au><au>Dos Santos, Renato A C</au><au>Bowyer, Paul</au><au>Bromley, Michael</au><au>Owens, Rebecca A</au><au>Doyle, Sean</au><au>Demasi, Marilene</au><au>Hernández, Diego C R</au><au>Netto, Luís Eduardo S</au><au>Pupo, Monica T</au><au>Rokas, Antonis</au><au>Loures, Flavio V</au><au>Wong, Koon H</au><au>Goldman, Gustavo H</au><au>Cramer, Robert A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>16</volume><issue>7</issue><spage>e1008645</spage><pages>e1008645-</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32667960</pmid><doi>10.1371/journal.ppat.1008645</doi><orcidid>https://orcid.org/0000-0002-7611-0201</orcidid><orcidid>https://orcid.org/0000-0002-7248-6551</orcidid><orcidid>https://orcid.org/0000-0002-9264-5118</orcidid><orcidid>https://orcid.org/0000-0002-1125-2399</orcidid><orcidid>https://orcid.org/0000-0002-2986-350X</orcidid><orcidid>https://orcid.org/0000-0003-0702-5465</orcidid><orcidid>https://orcid.org/0000-0001-6545-1978</orcidid><orcidid>https://orcid.org/0000-0002-4250-9177</orcidid><orcidid>https://orcid.org/0000-0001-9996-0105</orcidid><orcidid>https://orcid.org/0000-0001-9782-437X</orcidid><orcidid>https://orcid.org/0000-0002-3782-3698</orcidid><orcidid>https://orcid.org/0000-0002-8436-595X</orcidid><orcidid>https://orcid.org/0000-0002-0143-6557</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7374 |
| ispartof | PLoS pathogens, 2020-07, Vol.16 (7), p.e1008645 |
| issn | 1553-7374 1553-7366 1553-7374 |
| language | eng |
| recordid | cdi_plos_journals_2434497378 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Public Library of Science (PLoS) Journals Open Access; PubMed Central |
| subjects | Animal models Animals Aspergillosis Aspergillosis - metabolism Aspergillosis - microbiology Aspergillus Aspergillus fumigatus Aspergillus fumigatus - metabolism Aspergillus fumigatus - pathogenicity Bioinformatics Biology Biology and Life Sciences Biosynthesis Clusters Cytokines Defects Enzymes Fungal infections Fungal Proteins - metabolism Fungi Gene expression Gene Expression Regulation, Fungal - physiology Genes Genetic aspects Genomics Gliotoxin Gliotoxin - biosynthesis Granulocytes Health aspects Health sciences Homology Immune response Immune system Immunomodulation Kinases Medicine Medicine and Health Sciences Metabolites Mice Model testing Neutrophils Opportunist infection Oxidation resistance Oxidative stress Oxidative Stress - physiology Oxidoreductase Pathogens Pharmaceutical sciences Phylogeny Secondary metabolites Transcription factors Transcription Factors - metabolism Virulence Virulence - physiology |
| title | The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T09%3A54%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Aspergillus%20fumigatus%20transcription%20factor%20RglT%20is%20important%20for%20gliotoxin%20biosynthesis%20and%20self-protection,%20and%20virulence&rft.jtitle=PLoS%20pathogens&rft.au=Ries,%20Laure%20N%20A&rft.date=2020-07-01&rft.volume=16&rft.issue=7&rft.spage=e1008645&rft.pages=e1008645-&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1008645&rft_dat=%3Cgale_plos_%3EA631237490%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2434497378&rft_id=info:pmid/32667960&rft_galeid=A631237490&rft_doaj_id=oai_doaj_org_article_a8f50cb4322d4e79bd71b302c6284ecd&rfr_iscdi=true |