Ricin B lectin-like proteins mediate thermotolerance, cell wall integrity, and fungal virulence in Cryptococcus...

Cryptococcus neoformans is an important human fungal pathogen. Cell surface proteins mediate Cryptococcus-host interactions and play critical roles in fungal virulence. Proteins containing ricin B lectin-like domains (RBD) are involved in pathogen infection by interacting with exposed galactose residues of receptors on host cell surface. In this study, we screened the C. neoformans genome to identify proteins containing the ricin B lectin-like domain and identified five proteins that possess both a ricin B domain and a signal peptide. All five proteins contribute to cell wall integrity, particularly under high temperature. Four of these proteins localize to the cell wall and two are secreted to the culture medium. Expression of the RBD genes is positively regulated by the calcineurin-Crz1 pathway at host temperature. Furthermore, overexpression of either RBD2 or RBD5 restored the thermotolerance of the crz1Δ mutant to wild type levels. A comprehensive phenotypic analysis of these mutants revealed that Rbd proteins are involved in diverse functions, including the production of virulence factors, cell membrane and cell wall integrity, pathogen-host interactions, and fungal virulence in C. neoformans. This study enhances our understanding of the functions of Rbd proteins in fungal development and pathogenesis.