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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384679/
https://www.ncbi.nlm.nih.gov/pubmed/32667960
http://dx.doi.org/10.1371/journal.ppat.1008645
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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_facet 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 Ries, Laure N. A.
collection PubMed
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.
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spelling pubmed-73846792020-08-05 The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence 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. PLoS Pathog Research Article 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. Public Library of Science 2020-07-15 /pmc/articles/PMC7384679/ /pubmed/32667960 http://dx.doi.org/10.1371/journal.ppat.1008645 Text en © 2020 Ries et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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.
The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence
title The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence
title_full The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence
title_fullStr The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence
title_full_unstemmed The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence
title_short The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence
title_sort aspergillus fumigatus transcription factor rglt is important for gliotoxin biosynthesis and self-protection, and virulence
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384679/
https://www.ncbi.nlm.nih.gov/pubmed/32667960
http://dx.doi.org/10.1371/journal.ppat.1008645
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