Laccase Affects the Rate of Cryptococcus neoformans Nonlytic Exocytosis from Macrophages
Stefânia de Oliveira Frazão, Herdson Renney de Sousa, Lenise Gonçalves da Silva, Jéssica dos Santos Folha, Kaio César de Melo Gorgonha, Getúlio Pereira de Oliveira, Maria Sueli Soares Felipe, Ildinete Silva-Pereira, Arturo Casadevall, André Moraes Nicola, Patrícia Albuquerque
Abstract
Cryptococcus neoformans is a yeast that causes severe disease, primarily in immunosuppressed people. It has many attributes that allow it to survive and cause disease, such as a polysaccharide capsule and the dark pigment melanin produced by the laccase enzyme. Upon infection, the yeast is ingested by cells called macrophages, whose function is to kill them. Instead, these fungal cells can exit from macrophages in a process called nonlytic exocytosis. We know that this process is controlled by both host and fungal factors, only some of which are known. As part of an ongoing study, we observed that C. neoformans isolates that produce melanin faster are more-frequent targets of nonlytic exocytosis. Further experiments showed that this is probably due to higher production of laccase, because fungi lacking this enzyme are nonlytically exocytosed less often. This shows that laccase is an important signal/regulator of nonlytic exocytosis of C. neoformans from macrophages.