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Title: A DEVELOPMENTALLY REGULATED GENE CLUSTER INVOLVED IN CONIDIAL PIGMENT BIOSYNTHESIS IN ASPERGILLUS FUMIGATUS

Author
item ROMERO, R
item GUERRERO, A
item Wheeler, Michael - Mike
item TORRES, H

Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/23/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary: The bluish-green fungus Aspergillus fumigatus is an important human disease-causing organism or pathogen. It produces bluish-green spores that are responsible for infection and usually only infect people with weakened immune (disease resistance) systems. The bluish green pigment in spores of this fungus have recently been shown to influence the ability of this fungus to cause serious disease in mice. In the present study, six genes in a cluster were identified as being responsible for production of the bluish-green pigment in spores of the fungus. These genes were studied and characterized and their relationship with enzymes and compounds involved in pigment synthesis was established. The significance of this work is that we have a better understanding of how these pigments are made in A. fumigatus. This information will be used to better understand the role of this type of pigmentation as a factor in causing disease.

Technical Abstract: Aspergillus fumigatus, a filamentous fungus producing bluish-green conidia, is an important opportunistic pathogen primarily affecting immunocompromised patients. Conidial pigmentation of A. fumigatus has been shown to influence its virulence significantly in a murine model. In the present study, six genes, forming a gene cluster spanning 19kb, were identified as being responsible for conidial pigment biosynthesis in A. fumigatus. Northern blot analyses showed that the six genes were developmentally regulated, being expressed during conidiation. Genes alb1 (albino 1), arp 1 (aspergillus reddish pink 1), and arp2 had great similarity with polyketide syntheses, scytalone dehydratases, and hydroxynaphthalene (HN) reductases respectively found in the dihydroxynaphthalene (DHN)-melanin pathway of brown to black fungi. Gene abr1 (aspergillus brown 1) possessed two mutlicopper oxydase signatures. Gene abr2 shared homology with Aspergillus nidulans yA, which encoes a laccase. The presence of a DHN-melanin pathway in A. fumigatus was supported by the fact that scytalone and flaviolin were accumulated by the arp1 disruptant whereas only flaviolin was accumulated by the arp2 disruptants. Scytalone and flaviolin are well-known metabolites of the DHN-melanin pathway in other fungi. In addition, the wild-type strain and the arp1 disruptant only accumulated flaviolin when they were treated with tricyclazole, a fungicide that specifically inhibits HN reductases involved in the DHN-melanin pathway. Based on DNA sequence similarity and biochemical analyses, we conclude that the 19 kb DNA fragment contains a six-gene cluster, which is required for conidial pigment biosynthesis in A. fumigatus.