The Aspergillus fumigatus conidial melanin production is regulated by the bifunctional bHLH DevR and MADS‐box RlmA transcription factors

Abstract

Melanins play a crucial role in defending organisms against external stressors. In several pathogenic fungi, including the human pathogen Aspergillus fumigatus, melanin production was shown to contribute to virulence. A. fumigatus produces two different types of melanins, i.e., pyomelanin and dihydroxynaphthalene (DHN)-melanin. DHN-melanin forms the gray-green pigment characteristic for conidia, playing an important role in immune evasion of conidia and thus for fungal virulence. The DHN-melanin biosynthesis pathway is encoded by six genes organized in a cluster with the polyketide synthase gene pksP as a core element. Here, cross-species promoter analysis identified specific DNA binding sites in the DHN-melanin biosynthesis genes pksP-arp1 intergenic region that can be recognized by bHLH and MADS-box transcriptional regulators. Independent deletion of two genes coding for the transcription factors DevR (bHLH) and RlmA (MADS-box) interfered with sporulation and reduced the expression of the DHN-melanin gene cluster. In vitro and in vivo experiments proved that these transcription factors cooperatively regulate pksP expression acting both as repressors and activators in a mutually exclusive manner. The dual role executed by each regulator depends on specific DNA motifs recognized in the pksP promoter region.

The basic helix–loop–helix transcription factor Crf1 is required for development and pathogenicity of the rice blast fungus by regulating carbohydrate and lipid metabolism

“…In Aspergillus nidulans , Bh1 is involved in the regulation of penicillin biosynthesis and DevR is required for both asexual and sexual development (Caruso et al ., ; Tuncher et al ., ). In Aspergillus fumigatus , DevR regulated dihydroxynaphthalene (DHN)‐melanin synthesis (Valiante et al ., ), and SrbA is critial for cell polarity, hypoxia adaptation, and virulence (Willger et al ., ; Dhingra et al ., ). In Aspergillus oryzae , SclR promotes sclerotial formation and EcdR is involved in the early stages of conidiophore development (Jin et al ., ).…”

The Basic-Region Helix-Loop-Helix Transcription Factor DevR Significantly Affects Polysaccharide Metabolism in Aspergillus oryzae

“…However, the deletion caused wrinkled colonies and resulted in a yellow pigment, and the strain did not form conidia on minimal agar plates. Additionally, DevR also regulates conidial melanin production in Aspergillus fumigatus (19). As an essential component of the cell wall, melanin plays a significant role in protecting organisms from external stresses (20).…”

“…Among these genes, pksP, a polyketide synthase gene, plays a core role. It has been reported that DevR and another MADS box transcription factor, RlmA, may bind to the pksP promoter to induce the transcription activity of pksP, thus regulating melanin production (19).…”

“…Analysis of the protein-DNA interaction. Recent research shows that bHLH transcription factors recognize specific DNA sites named E boxes, which are characterized by a (G/C)CANNTG(G/C) sequence (19). In addition, it was reported that DevR binds to the E-box sites in the pksP promoter region (19).…”

“…Recent research shows that bHLH transcription factors recognize specific DNA sites named E boxes, which are characterized by a (G/C)CANNTG(G/C) sequence (19). In addition, it was reported that DevR binds to the E-box sites in the pksP promoter region (19). In this study, to verify whether the DevR protein interacts with the promoters of some chitin and starch metabolismrelated genes, we first analyzed the promoter regions of these genes, some of which contain putative E-box sites within the 1.0-kb promoter regions (Table 1).…”