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 ctpA⏠conidia elicited much stronger immune responses from the infected invertebrate host Galleria mellonella than the pigmented ctpA⏠or wild-type conidia. Such enhancement in eliciting Galleria immune responses was independent of the ctpA⏠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.A spergillus fumigatus is an opportunistic pathogen that causes life-threatening invasive disease in immunocompromised hosts (1). Its asexual spores, named conidia, are the initial source of inocula for infection and are the vehicles for dispersal and survival. Under favorable conditions, conidia break dormancy and grow as elongated, highly polarized hyaline hyphae. Upon achieving competency and exposure to air, hyphae produce aerial conidiophore stalks and develop elaborate multicellular conidiophores that generate chains of melanized uninucleate conidia (2, 3) (Fig. 1A and B). BrlA, a C 2 H 2 zinc finger transcription factor, is the master regulator that controls the initiation of conidiophore development in Aspergillus (4, 5). AbaA and WetA, two other important regulators that function downstream of BrlA, are required for proper progression of conidiation (6). The abaA gene is activated during the middle stage of conidiophore development, while the wetA gene is required for the activation of late conidiation-specific genes.The 1,8-dihydroxynaphthalene (DHN) melanin coating A. fumigatus conidia gives them their characteristic bluish green color (Fig. 1B). Melanin is an amorphous polymer that is produced by a variety of microbes and ...