Role of cell surface molecules of Blastomyces dermatitidis in the pathogenesis and immunobiology of blastomycosis.
The cell surface of pathogenic microbes is critical in directing their interactions with the host. The discovery of a 120 kd antigen/adhesin WI-1 on the yeast or parasitic form of Blastomyces dermatitidis has elucidated the molecular basis of host/pathogen interactions in blastomycosis. WI-1 has three structural domains: (1) an N-terminal hydrophobic domain that spans the cell membrane, (2) a C-terminal epidermal growth factor-like domain that may bind extracellular matrix, and (3) a central domain of many 24- or 25 amino-acid repeats arrayed in tandem. The repeat is homologous to invasin, a Yersinia adhesin, and binds CD11b/CD18 (CR3) and CD14 receptors on host cells. WI-1 expression is altered on genetically related strains of B dermatitidis differing in virulence and modulates how hypovirulent mutants interact with macrophages. WI-1 also evokes humoral and cell-mediated immune responses in acquired resistance to B dermatitidis that may help clear the fungus in the host. These observations on WI-1 provide new insight into a key pathogenic factor and antigen of the fungus and may ultimately help in designing new ways to diagnose, treat, and prevent blastomycosis.
Klein
B S
BS
Department of Pediatrics, University of Wisconsin Medical School, Madison, USA.
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology; D001758:Blastomyces / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D001759:Blastomycosis / Q000276:immunology / Q000382:microbiology*; D005656:Fungal Proteins; D005936:Glucans / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000382:microbiology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D011650:Pulmonary Alveoli / Q000382:microbiology; D014774:Virulence / Q000235:genetics
D000954:Antigens, Surface; D005656:Fungal Proteins; D005936:Glucans; D006023:Glycoproteins; D008562:Membrane Glycoproteins; C045788:alpha-1,3-glucan