The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence
dc.contributor.author | Ries, LNA | |
dc.contributor.author | Pardeshi, L | |
dc.contributor.author | Dong, Z | |
dc.contributor.author | Tan, K | |
dc.contributor.author | Steenwyk, JL | |
dc.contributor.author | Colabardini, AC | |
dc.contributor.author | Ferreira Filho, JA | |
dc.contributor.author | de Castro, PA | |
dc.contributor.author | Silva, LP | |
dc.contributor.author | Preite, NW | |
dc.contributor.author | Almeida, F | |
dc.contributor.author | de Assis, LJ | |
dc.contributor.author | dos Santos, RAC | |
dc.contributor.author | Bowyer, P | |
dc.contributor.author | Bromley, M | |
dc.contributor.author | Owens, RA | |
dc.contributor.author | Doyle, S | |
dc.contributor.author | Demasi, M | |
dc.contributor.author | Hernández, DCR | |
dc.contributor.author | Netto, LES | |
dc.contributor.author | Pupo, MT | |
dc.contributor.author | Rokas, A | |
dc.contributor.author | Loures, FV | |
dc.contributor.author | Wong, KH | |
dc.contributor.author | Goldman, GH | |
dc.date.accessioned | 2020-07-17T07:44:48Z | |
dc.date.issued | 2020-07-15 | |
dc.description.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. | en_GB |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP | en_GB |
dc.description.sponsorship | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) | en_GB |
dc.description.sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | University of Macau | en_GB |
dc.description.sponsorship | National Science Foundation (NSF) | en_GB |
dc.description.sponsorship | Vanderbilt University | en_GB |
dc.description.sponsorship | Howard Hughes Medical Institute | en_GB |
dc.identifier.citation | Vol. 16 (7), article e1008645 | en_GB |
dc.identifier.doi | 10.1371/journal.ppat.1008645 | |
dc.identifier.grantnumber | 2017/14159-2 | en_GB |
dc.identifier.grantnumber | 2016/07870-9 | en_GB |
dc.identifier.grantnumber | 2017/01188-4 | en_GB |
dc.identifier.grantnumber | 2013/50954-0 | en_GB |
dc.identifier.grantnumber | 2018/25217-6 | en_GB |
dc.identifier.grantnumber | 2014/00789-6 | en_GB |
dc.identifier.grantnumber | 2018-14762-3 | en_GB |
dc.identifier.grantnumber | 2017/21983-3 | en_GB |
dc.identifier.grantnumber | 2013/07937-8 | en_GB |
dc.identifier.grantnumber | 2019/09278-8 | en_GB |
dc.identifier.grantnumber | 2016/03322-7 | en_GB |
dc.identifier.grantnumber | 2017/07536-4 | en_GB |
dc.identifier.grantnumber | 301058/2019-9 | en_GB |
dc.identifier.grantnumber | 404735/2018-5 | en_GB |
dc.identifier.grantnumber | 303792/2018-2 | en_GB |
dc.identifier.grantnumber | 001 | en_GB |
dc.identifier.grantnumber | 208396/Z/17/Z | en_GB |
dc.identifier.grantnumber | MYRG2018-00017-FHS | en_GB |
dc.identifier.grantnumber | DEB-1442113 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/121987 | |
dc.language.iso | en | en_GB |
dc.publisher | Public Library of Science (PLoS) | en_GB |
dc.rights | © 2020 Ries et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_GB |
dc.title | The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-07-17T07:44:48Z | |
dc.description | This is the final version (corrected proof). The final published version is available from Public Library of Science via the DOI in this record | en_GB |
dc.description | Data Availability: Short reads were submitted to the NCBI’s Sequence Read Archive under accession number SRP154617 (https://www.ncbi.nlm.nih.gov/sra/?term=SRP154617). The ChIPseq data are available from NCBI SRA (sequence read archive) database under accession number PRJNA574873 (https://www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA574873&o=acc_s%3Aa). | en_GB |
dc.identifier.eissn | 1553-7374 | |
dc.identifier.journal | PLOS Pathogens | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-05-19 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-05-19 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-07-17T07:36:25Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-07-17T07:44:52Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © 2020 Ries et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.