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PMID:24123270

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Citation

Upadhyay, S, Torres, G and Lin, X (2013) Laccases involved in 1,8-dihydroxynaphthalene melanin biosynthesis in Aspergillus fumigatus are regulated by developmental factors and copper homeostasis. Eukaryotic Cell 12:1641-52

Abstract

Aspergillus fumigatus produces heavily melanized infectious conidia. The conidial melanin is associated with fungal virulence and resistance to various environmental stresses. This 1,8-dihydroxynaphthalene (DHN) melanin is synthesized by enzymes encoded in a gene cluster in A. fumigatus, including two laccases, Abr1 and Abr2. Although this gene cluster is not conserved in all aspergilli, laccases are critical for melanization in all species examined. Here we show that the expression of A. fumigatus laccases Abr1/2 is upregulated upon hyphal competency and drastically increased during conidiation. The Abr1 protein is localized at the surface of stalks and conidiophores, but not in young hyphae, consistent with the gene expression pattern and its predicted role. The induction of Abr1/2 upon hyphal competency is controlled by BrlA, the master regulator of conidiophore development, and is responsive to the copper level in the medium. We identified a developmentally regulated putative copper transporter, CtpA, and found that CtpA is critical for conidial melanization under copper-limiting conditions. Accordingly, disruption of CtpA enhanced the induction of abr1 and abr2, a response similar to that induced by copper starvation. Furthermore, nonpigmented ctpAΔ conidia elicited much stronger immune responses from the infected invertebrate host Galleria mellonella than the pigmented ctpAΔ or wild-type conidia. Such enhancement in eliciting Galleria immune responses was independent of the ctpAΔ conidial viability, as previously observed for the DHN melanin mutants. Taken together, our findings indicate that both copper homeostasis and developmental regulators control melanin biosynthesis, which affects conidial surface properties that shape the interaction between this pathogen and its host.

Links

PubMed PMC3889567 Online version:10.1128/EC.00217-13

Keywords

Aspergillus fumigatus/enzymology; Aspergillus fumigatus/genetics; Aspergillus fumigatus/growth & development; Aspergillus fumigatus/metabolism; Copper/metabolism; Fungal Proteins/genetics; Fungal Proteins/metabolism; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Fungal; Hyphae/enzymology; Hyphae/genetics; Hyphae/growth & development; Laccase/genetics; Laccase/metabolism; Melanins/biosynthesis; Naphthols; Spores, Fungal/enzymology; Spores, Fungal/genetics; Spores, Fungal/growth & development

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

ASPFU:Q4WQF3

acts_upstream_of_or_within

GO:0043324: pigment metabolic process involved in developmental pigmentation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ASPFM:Q9UVV2

GO:0071944: cell periphery

ECO:0000314:

C

Figure 3 shows Abr1-GFP is observed on the cell surface of aerial hyphae, vesicles, phialides, and conidia.

complete
CACAO 11729

Notes

See also

References

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