The developmentally regulated alb1 gene of Aspergillus fumigatus: its role in modulation of conidial morphology and virulence

• Published in: Journal of bacteriology 1998-06, Vol.180 (12), p.3031-3038
• Main Authors: Tsai, H.F. (National Institute of Allergy and Infectious Diseases, Bethesda, MD.), Chang, Y.C, Washburn, R.G, Wheeler, M.H, Kwon-Chung, K.J
• Format: Article
• Language: English
• Subjects: ACILTRANSFERASA; ACYLTRANSFERASE; ACYLTRANSFERASES; Allergies; Amino Acid Sequence; AMINO ACID SEQUENCES; ARN MENSAJERO; ARN MESSAGER; ASPERGILLUS FUMIGATUS; Aspergillus fumigatus - genetics; Aspergillus fumigatus - growth & development; Aspergillus fumigatus - pathogenicity; Bacteria; Bacteriology; Base Sequence; BINDING; BIOSINTESIS; BIOSYNTHESE; BIOSYNTHESIS; CHEMICAL COMPOSITION; Cloning, Molecular; COMPLEMENT; Complement C3 - metabolism; COMPLEMENTATION; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; CONIDIATION; DNA, Fungal - genetics; ESPORAS FUNGICAS; ESPORULACION; Eukaryotic Cells; EXPERIMENTACION IN VIVO; EXPERIMENTAL INFECTION; EXPERIMENTATION IN VIVO; EXPRESION GENICA; EXPRESSION DES GENES; FACTEUR IMMUNOLOGIQUE; FACTORES INMUNOLOGICOS; FAGOCITOS; FUNGAL SPORES; Fungi; GENBANK/AF025541; GENE; GENE EXPRESSION; Gene Expression Regulation, Developmental; Gene Expression Regulation, Fungal; GENES; Genes, Fungal; GENETICA; GENETICS; GENETIQUE; GRANULOCITOS; GRANULOCYTE; GRANULOCYTES; Humans; IMMUNOLOGICAL FACTORS; In Vitro Techniques; IN VIVO EXPERIMENTATION; INFECCION EXPERIMENTAL; INFECTION EXPERIMENTALE; MELANINAS; MELANINE; MELANINS; Melanins - biosynthesis; MESSENGER RNA; MICE; Microscopy, Electron, Scanning; MOLECULAR SEQUENCE DATA; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; MUTANT; MUTANTES; MUTANTS; Naphthols - metabolism; NEUTROPHILS; Neutrophils - immunology; NUCLEOTIDE SEQUENCE; PATHOGENICITY; PATOGENICIDAD; PHAGOCYTE; PHAGOCYTES; PHAGOCYTOSIS; Phenotype; PIGMENTACION; PIGMENTATION; Pigmentation - genetics; Pigmentation - physiology; POLYKETIDE SYNTHASE; POUVOIR PATHOGENE; RATON; SECUENCIA NUCLEOTIDICA; Sequence Homology, Amino Acid; SEQUENCE NUCLEOTIDIQUE; SOURIS; SPORE FONGIQUE; SPORULATION; STRUCTURAL GENES; Virulence - genetics
• ISSN: 0021-9193; 1098-5530
• DOI: 10.1128/JB.180.12.3031-3038.1998

Aspergillus fumigatus, an important opportunistic pathogen which commonly affects neutropenic patients, produces conidia with a bluish-green color. We identified a gene, alb1, which is required for conidial pigmentation. The alb1 gene encodes a putative polyketide synthase, and disruption of alb1 resulted in an albino conidial phenotype. Expression of alb1 is developmentally regulated, and the 7-kb transcript is detected only during the conidiation stage. The alb1 mutation was found to block 1,3,6,8-tetrahydroxpnaphtthalene production, indicating that alb1 is involved in dihydroxynaphthalene-melanin biosynthesis. Scanning electron microscopy studies showed that the alb1 disruptant exhibited a smooth conidial surface, whereas, complementation of the alb1 deletion restored the echinulate wild-type surface. Disruption of alb1 resulted in a significant increase in C3 binding on conidial surfaces, and the conidia of the alb1 disruptant were ingested by human neutrophils at a higher rate than were those of the wild type. The alb1-complemented strain producing bluish-green conidia exhibited inefficient C3 binding and neutrophil-mediated phagocytosis quantitatively similar to those of the wild type. Importantly, the alb1 disruptant had a statistically significant loss of virulence compared to the wild-type and alb1-complemented strains in a murine model. Then results suggest that disruption of alb1 causes pleiotropic effects on conidial morphology and fungal virulence