The transcription factor Pdr802 regulates Titan cell production and Cryptococcus neoformans pathogenicity

We report on our study the role of C. neoformans transcription factor Pdr802, whose expression is highly induced under host-like conditions in vitro and is critical for C. neoformans dissemination and virulence in a mouse model of infection. We found that direct targets of Pdr802 include the calcineurin targets Had1 and Pmc1, which are important for C. neoformans virulence, the transcription factor Bzp4, which promotes cryptococcal melanization and capsule thickness, and 35 transmembrane transporters. Notably, a strain engineered to lack Pdr802 showed a dramatically increased population of Titan cells. Since Titan cells are not phagocyted and do not disseminate via the Trojan horse mechanism or via penetration of biological barriers, this likely explains the reduced dissemination of pdr802 cells to the central nervous system and consequently reduced pathogenicity of this strain. The role of Pdr802 as a negative regulator of titanisation is thus critical for cryptococcal virulence. We studied the target of the C. neoformans transcription factor Pdr802