title: Effect of aeration on gliotoxin production by Aspergillus fumigatus in its culture filtrate.
abstract: Gliotoxin, one of the mycotoxins produced by Aspergillus fumigatus, has various, potent bioactivities. However, it has not been considered to be a toxic (or virulence) factor because of its slow production. The aim of the present study was to investigate the effects of aeration on the cytotoxicity of A. fumigatus culture filtrate, and to determine the optimal condition for the rapid production of gliotoxin from this fungus. Fungal culture filtrates were made in three different containers under various conditions of aeration and O2 concentration. These filtrates were compared in terms of their cytotoxicity on murine macrophages and analyzed by gas chromatography. The culture filtrate showed high cytotoxicity when it was made under highly aerated conditions, but it was significantly less cytotoxic when prepared under non-aerated conditions. The cytotoxic activity became evident within 15 h of culture at 20% O2, when the fungus had already started producing gliotoxin. The culture filtrates also contained some other as yet unidentified substances that might also to some extent contribute to the cytotoxicity. In light of these results, the authors propose that a highly aerated condition is responsible for the rapid production of gliotoxin, and that gliotoxin might play an important role in the respiratory infection by A. fumigatus, with other toxic substances acting additively or synergistically.
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Japan. fewata@restaff.chiba-u.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kamei
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Sekine
authors.forename: Mayumi
authors.initials: M
authors.lastname: Waku
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nishimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyaji
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuriyama
mesh_terms: D000332:Aerobiosis; D000818:Animals; D001232:Aspergillus fumigatus / Q000254:growth & development / Q000378:metabolism*; D003124:Colorimetry; D008401:Gas Chromatography-Mass Spectrometry; D005912:Gliotoxin / Q000096:biosynthesis*; D017737:Macrophages, Peritoneal / Q000382:microbiology*; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism
chemical_list: C476329:2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt; D013778:Tetrazolium Salts; D005912:Gliotoxin; D010100:Oxygen