The developmentally regulated alb1 gene of Aspergillus fumigatus: its role in modulation of conidial morphology and virulence.
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-tetrahydroxynaphthalene 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. These results suggest that disruption of alb1 causes pleiotropic effects on conidial morphology and fungal virulence.
Tsai
H F
HF
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Chang
Y C
YC
Washburn
R G
RG
Wheeler
M H
MH
Kwon-Chung
K J
KJ
D000595:Amino Acid Sequence; D001232:Aspergillus fumigatus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D001483:Base Sequence; D003001:Cloning, Molecular; D003176:Complement C3 / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006801:Humans; D066298:In Vitro Techniques; D008543:Melanins / Q000096:biosynthesis; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009284:Naphthols / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D010641:Phenotype; D010858:Pigmentation / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014774:Virulence / Q000235:genetics
D003176:Complement C3; D004271:DNA, Fungal; D008543:Melanins; D009097:Multienzyme Complexes; D009284:Naphthols; C041660:1,8-dihydroxynaphthalene