| Full text | |
| Author(s): Show less - |
Ries, Laure N. A.
[1]
;
Pardeshi, Lakhansing
[2, 3]
;
Dong, Zhicliang
[3]
;
Tan, Kaeling
[2, 3, 4]
;
Steenwyk, Jacob L.
[5]
;
Colabardini, Ana Cristina
[6]
;
Ferreira Filho, Jaire A.
[6]
;
de Castro, Patricia A.
[6]
;
Silva, Lilian P.
[6]
;
Preite, Nycolas W.
[7]
;
Almeida, Fausto
[1]
;
de Assis, Leandro J.
[6]
;
dos Santos, Renato A. C.
[6]
;
Bowyer, Paul
[8]
;
Bromley, Michael
[8]
;
Owens, Rebecca A.
[9]
;
Doyle, Sean
[9]
;
Demasi, Marilene
[10]
;
Hernandez, Diego C. R.
[6]
;
Netto, Luis Eduardo S.
[11]
;
Pupo, Monica T.
[6]
;
Rokas, Antonis
[5]
;
Loures, V, Flavio
;
Wong, Koon H.
[2, 12]
;
Goldman, Gustavo H.
[6]
Total Authors: 25
|
| Affiliation: Show less - | [1] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto - Brazil
[2] Univ Macau, Genom & Bioinformat Core, Fac Hlth Sci, Taipa, Macao - Peoples R China
[3] Univ Macau, Fac Hlth Sci, Taipa, Macao - Peoples R China
[4] Univ Macau, Ctr Precis Med & Res & Training, Taipa, Macao - Peoples R China
[5] Vanderbilt Univ, Dept Biol Sci, 221 Kirkland Hall, Nashville, TN 37235 - USA
[6] Univ Sao Paulo, Fac Pharmaceut Sci, Ribeirao Preto - Brazil
[7] V, Univ Sao Paulo, Inst Sci & Technol Fed, Sao Jose Dos Campos, SP - Brazil
[8] Univ Manchester, Fac Biol Med & Hlth, Manchester Fungal Infect Grp, Div Infect Immun & Resp Med, Sch Biol Sci, Manchester, Lancs - England
[9] Maynooth Univ, Dept Biol, Maynooth, Kildare - Ireland
[10] Inst Butantan, Lab Biochem & Biophys, Sao Paulo - Brazil
[11] Univ Sao Paulo, Inst Biosci, Sao Paulo - Brazil
[12] Univ Macau, Inst Translat Med, Taipa, Macao - Peoples R China
Total Affiliations: 12
|
| Document type: | Journal article |
| Source: | PLOS PATHOGENS; v. 16, n. 7 JUL 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
Aspergillus fumigatusis 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 eliminatingA.fumigatusduring invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important forA.fumigatusoxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of severalgligenes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding genegliT, 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 Aspergillusspecies. Author summary A.fumigatusis a prevalent opportunistic fungal pathogen that causes a wide range of diseases, in both immunocompetent and immunocompromised subjects. Contributing toA.fumigatusvirulence, is thein vivosecretion of gliotoxin, a mycotoxin with both immunosuppressive and immunomodulatory properties. Regulation of the gliotoxin-encoding biosynthetic gene cluster has proven to be a multifactorial and hierarchical process. In this work, we identify a transcription factor, named RglT (regulator of gliotoxin), that is crucial for gliotoxin biosynthesis and self-protection, a process that mainly occurs through the direct regulation of the oxidoreductase-encoding genegliT. The absence ofrglTresulted in a strain that was highly sensitive to oxidative stress, to exogenous gliotoxin and hypovirulent in a chemotherapeutic murine model of IPA. Furthermore, we show that homologues of both RglT and GliT co-exist within the class of eurotiomycetes and appear to be functionally conserved in non gliotoxin-producing fungal species. Our study therefore highlights the importance of mycotoxin self-protection in pathogenic and non-pathogenic fungal species with consequences for fungal virulence and survival. (AU) | |
| FAPESP's process: | 17/14159-2 - The role of lactose and acetate metabolism in Aspergillus fumigatus virulence |
| Grantee: | Laure Nicolas Annick Ries |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 17/21983-3 - Genomic analysis of Aspergillus cryptic species |
| Grantee: | Renato Augusto Corrêa dos Santos |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 18/25217-6 - Organization and integration of large scale data to study the dynamics of expression of MAP kinases of the fungus Aspergillus fumigatus in diverse genetic and environmental conditions |
| Grantee: | Jaire Alves Ferreira Filho |
| Support Opportunities: | Scholarships in Brazil - Technical Training Program - Technical Training |
| FAPESP's process: | 17/07536-4 - Molecular Mechanisms Involved in Paradoxal Growth Induced by Caspofungin in Aspergillus fumigatus |
| Grantee: | Ana Cristina Colabardini |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 17/01188-4 - Relationship of the Protozoan Crithidia spp with Bacterioma associated with the stingless Bee Melipona scutellaris: Chemical, Ecological and Pharmacological Studies |
| Grantee: | Diego Carlos Rodriguez Hernandez |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 13/50954-0 - Novos agentes terapeuticos obtidos de bacterias simbiontes de invertebrados brasileiros. (fapesp/fic-nih) |
| Grantee: | Mônica Tallarico Pupo |
| Support Opportunities: | BIOTA-FAPESP Program - Thematic Grants |
| FAPESP's process: | 14/00789-6 - Functional characterization of Aspergillus nidulans phosphatases involved on glucose metabolism |
| Grantee: | Leandro Jose de Assis |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 13/07937-8 - Redoxoma - Redox processes in biomedicine. |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 16/07870-9 - The influence of Mitogen Activated Protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence |
| Grantee: | Gustavo Henrique Goldman |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/09278-8 - The role of myeloid-derived suppressor cells (MDSCs) in murine paracoccidioidomycosis. |
| Grantee: | Nycolas Willian Preite |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 16/03322-7 - Role of galectin-3 in the Cryptococcus neoformans infection |
| Grantee: | Fausto Bruno dos Reis Almeida |
| Support Opportunities: | Research Grants - Young Investigators Grants |