title: Aspergillus fumigatus arp1 modulates conidial pigmentation and complement deposition.
abstract: Aspergillus fumigatus is an important pathogen causing invasive pulmonary aspergillosis in immunocompromised patients. The fungus propagates by conidia, which are the infectious structures inhaled by the human host. Opsonophagocytosis is thought to contribute to clearance of the inhaled conidia, a process that is facilitated by complement deposition on conidial surfaces. We now show that conidial colour mutants exhibit significant increases in C3 binding capacity compared with wild type. A reddish-pink mutation that led to enhanced C3 binding was complemented by a cosmid clone. A 3.3 kb DNA fragment from the subsequently rescued cosmid was sufficient to restore the bluish-green conidial pigment. The bluish-green transformant exhibited a level of C3 binding similar to that of the parental strain. A gene, designated arp1, was responsible for the complementation. Comparison of the genomic and cDNA sequences of arp1 revealed that it has two introns and encodes a putative protein of 168 amino acids. Arp1 is very similar to scytalone dehydratase, an enzyme involved in 1,8-dihydroxynaphthalene-melanin synthesis in Colletotrichum lagenarium and Magnaporthe grisea. Northern hybridization analysis revealed that arp1 is developmentally regulated, being expressed during conidiation. Disruption of arp1 resulted in reddish-pink conidia and increased C3 binding. Our studies suggest that arp1 modulates the bluish-green pigmentation of conidia as well as complement deposition.
authors.affiliation: Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: H F
authors.initials: HF
authors.lastname: Tsai
authors.forename: R G
authors.initials: RG
authors.lastname: Washburn
authors.forename: Y C
authors.initials: YC
authors.lastname: Chang
authors.forename: K J
authors.initials: KJ
authors.lastname: Kwon-Chung
mesh_terms: D000595:Amino Acid Sequence; D001232:Aspergillus fumigatus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015152:Blotting, Northern; D015139:Blotting, Southern; D003001:Cloning, Molecular; D003176:Complement C3 / Q000378:metabolism*; D003360:Cosmids / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D006836:Hydro-Lyases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010858:Pigmentation / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014170:Transformation, Genetic / Q000235:genetics
chemical_list: D003176:Complement C3; D005656:Fungal Proteins; C109850:Arp1 protein, Aspergillus fumagatus; D006836:Hydro-Lyases