title: VeA regulates conidiation, gliotoxin production, and protease activity in the opportunistic human pathogen Aspergillus fumigatus.
abstract: Invasive aspergillosis by Aspergillus fumigatus is a leading cause of infection-related mortality in immunocompromised patients. In this study, we show that veA, a major conserved regulatory gene that is unique to fungi, is necessary for normal morphogenesis in this medically relevant fungus. Although deletion of veA results in a strain with reduced conidiation, overexpression of this gene further reduced conidial production, indicating that veA has a major role as a regulator of development in A. fumigatus and that normal conidiation is only sustained in the presence of wild-type VeA levels. Furthermore, our studies revealed that veA is a positive regulator in the production of gliotoxin, a secondary metabolite known to be a virulent factor in A. fumigatus. Deletion of veA resulted in a reduction of gliotoxin production with respect to that of the wild-type control. This reduction in toxin coincided with a decrease in gliZ and gliP expression, which is necessary for gliotoxin biosynthesis. Interestingly, veA also influences protease activity in this organism. Specifically, deletion of veA resulted in a reduction of protease activity; this is the first report of a veA homolog with a role in controlling fungal hydrolytic activity. Although veA affects several cellular processes in A. fumigatus, pathogenicity studies in a neutropenic mouse infection model indicated that veA is dispensable for virulence.
authors.affiliation: Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois, USA.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Dhingra
authors.forename: David
authors.initials: D
authors.lastname: Andes
authors.forename: Ana M
authors.initials: AM
authors.lastname: Calvo
mesh_terms: D001232:Aspergillus fumigatus / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005912:Gliotoxin / Q000096:biosynthesis* / Q000633:toxicity; D010447:Peptide Hydrolases / Q000378:metabolism*; D013172:Spores, Fungal / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; D005912:Gliotoxin; D010447:Peptide Hydrolases