title: Aspergillus fumigatus CalA binds to integrin α5β1and mediates host cell invasion.
abstract: Aspergillus fumigatus is an opportunistic fungal pathogen that invades pulmonary epithelial cells and vascular endothelial cells by inducing its own endocytosis, but the mechanism by which this process occurs is poorly understood. Here, we show that the thaumatin-like protein CalA is expressed on the surface of the A. fumigatus cell wall, where it mediates invasion of epithelial and endothelial cells. CalA induces endocytosis in part by interacting with integrin α5β1on host cells. In corticosteroid-treated mice, a ΔcalA deletion mutant has significantly attenuated virulence relative to the wild-type strain, as manifested by prolonged survival, reduced pulmonary fungal burden and decreased pulmonary invasion. Pretreatment with an anti-CalA antibody improves survival of mice with invasive pulmonary aspergillosis, demonstrating the potential of CalA as an immunotherapeutic target. Thus, A. fumigatus CalA is an invasin that interacts with integrin α5β1on host cells, induces endocytosis and enhances virulence.
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Departments of Medicine, Microbiology and Immunology, McGill University Health Centre Research Institute, Montreal, Quebec H4A3J1, Canada.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Norma V
authors.initials: NV
authors.lastname: Solis
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Quynh T
authors.initials: QT
authors.lastname: Phan
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Swidergall
authors.affiliation: Departments of Medicine, Microbiology and Immunology, McGill University Health Centre Research Institute, Montreal, Quebec H4A3J1, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ralph
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.|David Geffen School of Medicine at UCLA, Los Angeles, California 90024, USA.
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.affiliation: Departments of Medicine, Microbiology and Immunology, McGill University Health Centre Research Institute, Montreal, Quebec H4A3J1, Canada.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Sheppard
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.|David Geffen School of Medicine at UCLA, Los Angeles, California 90024, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
mesh_terms: D000072283:A549 Cells; D000818:Animals; D001232:Aspergillus fumigatus / Q000472:pathogenicity* / Q000502:physiology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D054884:Host-Pathogen Interactions; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008168:Lung / Q000382:microbiology; D051379:Mice; D011485:Protein Binding; D055732:Pulmonary Aspergillosis / Q000382:microbiology / Q000473:pathology; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D039081:Integrin alpha5beta1; D037521:Virulence Factors