title: Increased production of gliotoxin is related to the formation of biofilm by Aspergillus fumigatus: an immunological approach.
abstract: Gliotoxin (GT) belongs to the epipolythiodioxopiperazine class of toxins secreted from certain fungi including Aspergillus fumigatus, which is the most prolific producer of this secondary metabolite. Recently, enhanced amounts of GT were found in in vitro biofilm-grown A. fumigatus mycelium. To further correlate the A. fumigatus biofilm growth phenotype with the enhanced secretion of GT, a polyclonal antibody (pAb) was produced by immunizing mice against GT. By an indirect immunofluorescent assay, pAb was then able to recognize specifically GT onto A. fumigatus Af293 biofilm formed on human pulmonary epithelial cells. Then, treating Af293 biofilms with a compound which reduces the GT disulfide bonds provoked shutdown of the GT-specific immunofluorescence (IF) signals along the hyphae. To explore the potential of GT for diagnostic use, pAb was shown to react with GT on hyphae into Aspergillus culture-positive respiratory tract specimens from patients with probable invasive aspergillosis (IA) and into tissue specimens from the lungs of patients with proven IA. As the presence of fungal hyphae in clinical specimens strongly indicates the in vivo A. fumigatus growth as a biofilm, anti-GT antibodies could be a specific and sensitive diagnostic tool for detecting A. fumigatus biofilm-associated clinical infections.
authors.affiliation: Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bugli
authors.forename: Francesco
authors.initials: F
authors.lastname: Paroni Sterbini
authors.forename: Margherita
authors.initials: M
authors.lastname: Cacaci
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martini
authors.forename: Stefano
authors.initials: S
authors.lastname: Lancellotti
authors.forename: Egidio
authors.initials: E
authors.lastname: Stigliano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Torelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Arena
authors.forename: Morena
authors.initials: M
authors.lastname: Caira
authors.forename: Patrizia
authors.initials: P
authors.lastname: Posteraro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.forename: Brunella
authors.initials: B
authors.lastname: Posteraro
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000502:physiology*; D018441:Biofilms / Q000254:growth & development*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D005912:Gliotoxin / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D025301:Hyphae; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D020545:Respiratory Mucosa / Q000382:microbiology
chemical_list: D000908:Antibodies, Fungal; D005912:Gliotoxin
keywords: Aspergillus fumigatus; biofilm; fungal biofilm-associated infection; gliotoxin; immunofluorescent assay