Transcriptional Control of the Production of Aspergillus fumigatus Conidia-Borne Secondary Metabolite Fumiquinazoline C Important for Phagocytosis Protection

Author(s)

Rocha, Marina Campos ^[1] ; Tadini Marilhano Fabri, Joao Henrique ^[1] ; Silva, Lilian Pereira ^[2] ; Figueiredo Angolini, Celio Fernando ^[3] ; Bertolini, Maria Celia ^[4] ; da Cunha, Anderson Ferreira ^[1] ; Valiante, Vito ^[5] ; Goldman, Gustavo Henrique ^[2] ; Fill, Taicia Pacheco ^[6] ; Malavazi, Iran

Affiliation

^[1] Univ Fed Sao Carlos, Ctr Ciencias Biol & Saude, Dept Genet & Evolucao, Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, Ribeirao Preto - Brazil

^[3] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil

^[4] Univ Estadual Paulista, Inst Quim Araraquara, Dept Bioquim & Tecnol, Araraquara, SP - Brazil

^[5] Leibniz Inst Nat Prod Res & Infect Biol, Leibniz Res Grp Biobricks Microbial Nat Prod Synt, Hans Knoll Inst, Jena - Germany

^[6] Univ Estadual Campinas, Inst Quim, Campinas, SP - Brazil

• Document type: Journal article
• Source: Genetics; v. 218, n. 1 MAY 2021.
• Web of Science Citations: 0

Abstract

Aspergillus fumigatus produces diverse secondary metabolites whose biological functions and regulation remain to be understood. Despite the importance of the conidia for this fungus, the role of the conidia-born metabolite fumiquinazoline C (FqC) is unclear. Here, we describe a dual function of the cell-wall integrity pathway in regulating FqC biosynthesis dictated by the MAPK kinase MpkA, which phosphorylates one of the nonribosomal peptide synthetases enzymes of the cluster (FmqC), and the transcription factor RlmA, which directly regulates the expression of fmq genes. Another level of crosstalk between the FqC regulation and the cell physiology is described since the deletion of the stress-responsive transcription factor sebA provokes derepression of the fmq cluster and overproduction of FqC. Thus, we describe a mechanism by which A. fumigatus controls FqC biosynthesis orchestrated by MpkA-RlmA and SebA and hence enabling survival and adaptation to the environmental niche, given that FqC is a deterrent of ameba predation. (AU)

• 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: 17/19694-3 - The role of heat shock proteins HsfA and Hsp90 and the regulator SmiA at cell wall integrity pathway activity in the opportunistic human pathogen Aspergillus fumigatus
• Grantee: Iran Malavazi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/17541-0 - Study of the relationship between genes involved in the cell wall integrity maintenance and thermotolerance in the human pathogenic fungi Aspergillus fumigatus
• Grantee: Iran Malavazi
• Support Opportunities: Regular Research Grants