title: Gliotoxin production by clinical and environmental Aspergillus fumigatus strains.
abstract: The mycotoxin gliotoxin is produced by fungi of the genus Aspergillus, including the important human pathogen Aspergillus fumigatus. Gliotoxin exerts a broad spectrum of immunosuppressive effects in vitro and is detectable in the sera of patients suffering from invasive aspergillosis. In order to correlate the pathogenic potential of A. fumigatus with the ability to produce gliotoxin and to investigate the taxonomic distribution of gliotoxin-producing Aspergillus strains among clinical isolates, a total of 158 Aspergillus isolates comprising four different species (A. fumigatus, n=100; A. terreus, n=27; A. niger, n=16; A. flavus, n=15) were collected from different medical centers (some originating from probable cases of aspergillosis) and from environmental samples in Germany and Austria. Remarkably, gliotoxin was detected in most culture filtrates of A. fumigatus of both clinical (98%) and environmental (96%) origin. The toxin was also detected, with decreasing frequency, in culture filtrates of A. niger (56%), A. terreus (37%), and A. flavus (13%). The highest gliotoxin concentrations were detected in A. fumigatus strains of clinical (max. 21.35 microg/ml, mean 5.75 microg/ml) and environmental (max. 26.25 microg/ml, mean 5.27 microg/ml) origin. Gliotoxin productivity of other Aspergillus species was significantly lower. Culture supernatants of A. fumigatus strains lacking gliotoxin production showed a significantly lower cytotoxicity on macrophage-like cells and T-cells in vitro. In contrast, lack of gliotoxin production in the other Aspergillus species tested had no significant influence on the cytotoxic effect of culture supernatant on these immune cells.
authors.affiliation: Faculty for Clinical Medicine Mannheim, University of Heidelberg, Institute for Medical Microbiology and Hygiene, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. claudio.kupfahl@imh.ma.uni-heidelberg.de
authors.forename: Claudio
authors.initials: C
authors.lastname: Kupfahl
authors.forename: Anna
authors.initials: A
authors.lastname: Michalka
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.forename: Guido
authors.initials: G
authors.lastname: Fischer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Haase
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruppert
authors.forename: Gernot
authors.initials: G
authors.lastname: Geginat
authors.forename: Herbert
authors.initials: H
authors.lastname: Hof
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000382:microbiology / Q000503:physiopathology; D001232:Aspergillus fumigatus / Q000254:growth & development / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D005800:Genes, Fungal; D005912:Gliotoxin / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D051379:Mice
chemical_list: D005912:Gliotoxin