The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence

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dc.contributorLab. Bioquímicapt_BR
dc.contributor.authorRies, Laure N. A.pt_BR
dc.contributor.authorPardeshi, Lakhansingpt_BR
dc.contributor.authorDong, Zhiqiangpt_BR
dc.contributor.authorTan, Kaelingpt_BR
dc.contributor.authorSteenwyk, Jacob L.pt_BR
dc.contributor.authorColabardini, Ana Cristinapt_BR
dc.contributor.authorFerreira Filho, Jaire A.pt_BR
dc.contributor.authorCastro, Patricia A. dept_BR
dc.contributor.authorSilva, Lilian P.pt_BR
dc.contributor.authorPreite, Nycolas W.pt_BR
dc.contributor.authorAlmeida, Faustopt_BR
dc.contributor.authorAssis, Leandro J. dept_BR
dc.contributor.authorSantos, Renato A. C. dospt_BR
dc.contributor.authorBowyer, Paulpt_BR
dc.contributor.authorBromley, Michaelpt_BR
dc.contributor.authorOwens, Rebecca A.pt_BR
dc.contributor.authorDoyle, Seanpt_BR
dc.contributor.authorDemasi, Marilenept_BR
dc.contributor.authorHernández, Diego C. R.pt_BR
dc.contributor.authorS. Netto, Luís Eduardopt_BR
dc.contributor.authorPupo, Monica T.pt_BR
dc.contributor.authorRokas, Antonispt_BR
dc.contributor.authorLoures, Flavio V.pt_BR
dc.contributor.authorWong, Koon H.pt_BR
dc.contributor.authorGoldman, Gustavo H.pt_BR
dc.date.accessioned2020-08-04T19:44:29Z-
dc.date.available2020-08-04T19:44:29Z-
dc.date.issued2020pt_BR
dc.identifier.citationRies LN.A., Pardeshi L, Dong Z, Tan K, Steenwyk JL., Colabardini AC, et al. The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence. PLoS. Pathog.. 2020 Jul;16(7):e1008645. doi:10.1371/journal.ppat.1008645.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/3105-
dc.description.abstractAspergillus 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.pt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorship(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.description.sponsorshipWellcome Trustpt_BR
dc.format.extente1008645pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofPLoS Pathogenspt_BR
dc.rightsOpen accesspt_BR
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_BR
dc.titleThe Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulencept_BR
dc.typeArticlept_BR
dc.rights.licenseCC BYpt_BR
dc.identifier.doi10.1371/journal.ppat.1008645pt_BR
dc.identifier.urlhttps://doi.org/10.1371/journal.ppat.1008645pt_BR
dc.contributor.external(USP) Universidade de São Paulopt_BR
dc.contributor.externalUniversity of Macau (UM)pt_BR
dc.contributor.externalVanderbilt Universitypt_BR
dc.contributor.external(UNIFESP) Universidade Federal de São Paulopt_BR
dc.contributor.externalUniversity of Manchesterpt_BR
dc.identifier.citationvolume16pt_BR
dc.identifier.citationissue7pt_BR
dc.relation.ispartofabbreviatedPLoS Pathogpt_BR
dc.identifier.citationabntv. 16 n. 7, e1008645, jul. 2020pt_BR
dc.identifier.citationvancouver2020 Jul;16(7):e1008645pt_BR
dc.contributor.butantanDemasi, Marilene|:Pesquisador|:Lab. Bioquímicapt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2017/14159-2pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2016/07870-9pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2017/01188-4pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2013/50954-0pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2018/25217-6pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2014/00789-6pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2018-14762-3pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2017/21983-3pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2013/07937-8pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2019/09278-8pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2016/03322-7pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2017/07536-4pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦301058/2019-9pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦404735/2018-5pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦303792/2018-2pt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior¦¦001pt_BR
dc.sponsorship.butantanWellcome Trust¦¦208396/Z/17/Zpt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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