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PMID: 9620950 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Journal of bacteriology ·Vol. 180 ·No. 12 ·1998-06-00 ·Pages 3031-8

Tsai HF, Chang YC, Washburn RG, Wheeler MH, Kwon-Chung KJ

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.

MeSH Terms
Amino Acid Sequence Aspergillus fumigatus/genetics,growth & development,pathogenicity Base Sequence Cloning, Molecular Complement C3/metabolism DNA, Fungal/genetics Gene Expression Regulation, Developmental Gene Expression Regulation, Fungal Genes, Fungal Humans In Vitro Techniques Melanins/biosynthesis Microscopy, Electron, Scanning Molecular Sequence Data Multienzyme Complexes/genetics,metabolism Naphthols/metabolism Neutrophils/immunology Phagocytosis Phenotype Pigmentation/genetics,physiology Sequence Homology, Amino Acid Virulence/genetics
Chemicals
Complement C3 DNA, Fungal Melanins Multienzyme Complexes Naphthols 1,8-dihydroxynaphthalene
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Tsai H F
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Chang Y C
Washburn R G
Wheeler M H
Kwon-Chung K J
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.180.12.3031-3038.1998
Published
1998-06-00
Pages
3031-8
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC107801
Subset
IM
Grants
NIAID NIH HHS · AI-01036 · United States
Databases
GENBANK
AF025541
External Links
PubMed source DOI: 10.1128/JB.180.12.3031-3038.1998 PMC Full Text View journal details
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