Aspergillus fumigatus CalA binds to integrin alpha(5)beta(1) and mediates host cell invasion

作者：Liu Hong; Lee Mark J; Solis Norma V; Phan Quynh T; Swidergall Marc; Ralph Benjamin; Ibrahim Ashraf S; Sheppard Donald C; Filler Scott G^*

来源：Nature Microbiology, 2017, 2(2): 16211.

DOI：10.1038/nmicrobiol.2016.211

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 alpha(5)beta(1) on host cells. In corticosteroid-treated mice, Delta calA 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 alpha(5)beta(1) on host cells, induces endocytosis and enhances virulence.

• 出版日期2017-2