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

ABSTRACT: 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.

SUBMITTER: Tsai HF

PROVIDER: S-EPMC107801 | biostudies-literature | 1998 Jun

REPOSITORIES: biostudies-literature

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

Tsai H F HF Chang Y C YC Washburn R G RG Wheeler M H MH Kwon-Chung K J KJ

Journal of bacteriology 19980601 12

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 ...[more]

PMID: 9620950

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Project description:Aspergillus fumigatus, a filamentous fungus producing bluish-green conidia, is an important opportunistic pathogen that primarily affects immunocompromised patients. Conidial pigmentation of A. fumigatus significantly influences its virulence in a murine model. In the present study, six genes, forming a gene cluster spanning 19 kb, were identified as involved in conidial pigment biosynthesis in A. fumigatus. Northern blot analyses showed the six genes to be developmentally regulated and expressed during conidiation. The gene products of alb1 (for "albino 1"), arp1 (for "aspergillus reddish-pink 1"), and arp2 have high similarity to polyketide synthases, scytalone dehydratases, and hydroxynaphthalene reductases, respectively, found in the dihydroxynaphthalene (DHN)-melanin pathway of brown and black fungi. The abr1 gene (for "aspergillus brown 1") encodes a putative protein possessing two signatures of multicopper oxidases. The abr2 gene product has homology to the laccase encoded by the yA gene of Aspergillus nidulans. The function of ayg1 (for "aspergillus yellowish-green 1") remains unknown. Involvement of the six genes in conidial pigmentation was confirmed by the altered conidial color phenotypes that resulted from disruption of each gene in A. fumigatus. The presence of a DHN-melanin pathway in A. fumigatus was supported by the accumulation of scytalone and flaviolin in the arp1 deletant, whereas only flaviolin was accumulated in the arp2 deletants. Scytalone and flaviolin are well-known signature metabolites of the DHN-melanin pathway. Based on DNA sequence similarity, gene disruption results, 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. However, the presence of abr1, abr2, and ayg1 in addition to alb1, arp1, and arp2 suggests that conidial pigment biosynthesis in A. fumigatus is more complex than the known DHN-melanin pathway.

Project description:Aerial conidia of Ascomycetes and Basidiomycetes are coated with an amphipathic hydrophobin layer commonly called rodlet layer, that renders their surface hydrophobic and resist wetting, thus facilitating effective dispersal in the air. Fungal hydrophobins are small secreted proteins with specific hydropathy patterns and eight cysteine residues ordered in a particular manner which define the two well characterized classes I and II of hydrophobins and a third intermediate class (Kershaw and Talbot, 1998. Littlejohn et al, 2012; Jensen et al, 2010). Wessels 1994). Class I assemblies are generally water insoluble, have an amyloid structure and form the patterned rodlet layer. Class II are smaller proteins than class I and are soluble in aqueous ethanol mixtures of SDS. The intermediate class is a rather heterogenous tote class which would gather non-class I and non-class II hydrophobins without a defined structure. In addition to the role of the rodlet in the fungal life during conidiogenesis and conidial dispersal in the air, it was shown that rodlets can have a role in fungal – host interactions and favour the pathogenic behavior of the fungal pathogens in humans, plant and insect hosts (Talbot et al., 1996, Aimanianda et al, 2009; Zhang et al, 2011). In Aspergillusfumigatus rodlets immunosilence the conidium and their loss from the conidial surface initiates the host immune response (Aimanianda et al., 2009). Our study is focused on the Rod A protein which forms the rodlet structure on the surface of the conidium of A. fumigatus. In spite of their prominent morphological and biological role, the molecular basis for rodlet self-assembly and desagregation in this fungal species has not been understood yet. Point mutations in the rodA gene have helped understanding the mechanism which drives hydrophobin proteins to assemble into highly ordered structures anchored to the conidium surface. Moreover, the biochemical events responsible for the lysis of the rodlets have been investigated.

Dataset Information

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

Publications

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

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