Specific interaction of Aspergillus fumigatus with fibrinogen and its role in cell adhesion.
Interaction between Aspergillus fumigatus conidia and different proteins known to mediate the attachment of malignant tumor cells or microorganisms to the host tissues was studied in vitro. Flow cytometry using fluorescein isothiocyanate-conjugated fibrinogen confirmed that binding of human fibrinogen to the conidia was dose dependent and specific. Binding was inhibited by unlabeled fibrinogen and by basement membrane laminin. Moreover, the expression of fibrinogen receptors at the surfaces of conidia seemed to be related to the maturation of the conidia. Binding sites appeared to be located in the D domains of the fibrinogen molecule. However, the peptide sequence recognized by the fungus could not be identified but was different from the classical adhesive recognition sequences, RGDS and fibrinogen gamma-chain dodecapeptide. In addition, an assay of adherence to proteins immobilized onto microtiter plates allowed us to establish the role of these interactions in fungal adhesion. Conidia strongly adhered to human fibrinogen and to laminin but not to fibronectin. Adhesion to fibrinogen substrates was specific, since it was inhibited by soluble fibrinogen and by specific antibodies, and seemed to be mediated by the D domains of the molecule. Study of the adhesion of numerous strains or clinical isolates to various mammalian fibrinogens did not reveal any particular affinity of strains for some animal species. Finally, by cultivation of the fungus in the presence of 125I-human fibrinogen and analysis of the radiolabeled material bound to the surface of the fungus, we were able to specify the sequence of events allowing its installation within the host. The interactions identified here may play an important role in governing fungal adherence and host tissue invasion.
Coulot
P
P
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire, Angers, France.
Bouchara
J P
JP
Renier
G
G
Annaix
V
V
Planchenault
C
C
Tronchin
G
G
Chabasse
D
D
D001232:Aspergillus fumigatus / Q000472:pathogenicity*; D001665:Binding Sites; D002448:Cell Adhesion; D005340:Fibrinogen / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D009842:Oligopeptides / Q000502:physiology
D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen