The Role of Ceramide Synthases in the Pathogenicity of Cryptococcus neoformans.
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ABSTRACT:
SUBMITTER: Munshi MA
PROVIDER: S-EPMC5839121 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Publications
The Role of Ceramide Synthases in the Pathogenicity of Cryptococcus neoformans.
Munshi Mansa A MA Gardin Justin M JM Singh Ashutosh A Luberto Chiara C Rieger Robert R Bouklas Tejas T Fries Bettina C BC Del Poeta Maurizio M
Cell reports 20180201 6
Cryptococcus neoformans (C. neoformans) is estimated to cause about 220,000 new cases every year in patients with AIDS, despite advances in antifungal treatments. C. neoformans possesses a remarkable ability to disseminate through an immunocompromised host, making treatment difficult. Here, we examine the mechanism of survival of C. neoformans under varying host conditions and find a role for ceramide synthase in C. neoformans virulence. This study also provides a detailed lipidomics resource fo ...[more]
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Project description: Not available
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Project description: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.
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