1051. The Cryptococcus neoformans Cuf1 Copper Metalloregulatory Transcription Factor
Session: Poster Abstract Session: Fungal Pathogenesis and Virulence
Saturday, October 22, 2011
Room: Poster Hall B1
Richard Festa*, Chen Ding, Dennis J. Thiele

Department of Pharmacology and Cancer Biology, Duke University Medical Center; Durham, NC, USA

Background: Copper is an important element for many cellular processes in most forms of life, however in excess copper can lead to toxicity through multiple mechanisms including oxidative stress through Fenton chemistry and the destruction of Fe-S clusters. Relevant to C. neoformans, copper is a cofactor for proteins implicated in virulence such as laccase and Cu/ZnSOD. C. neoformans must be able to aquire copper from the host, while maintaining sub-toxic concentrations. Copper homeostasis in C. neoformans is maintained bia the copper importers, Ctr1 and Ctr4, dedicated chaperones that route intracellular copper, and metallothioneins that bind and detoxify copper. Other fungi such as S. cerevisiae encode two copper responsive transcriptional activators, Mac1 and Ace1, to respond to copper deficiency and excess respectively. C. neoformans however encodes only one known copper responsive transcriptional regulator, Cuf1. C. neoformans is an emerging pathogen that causes fungal meningitis in immunocompromised patients, making a more efficacious treatment for this infection crucial. Methods: Target genes, such as Cuf1 were mutagenized using homologous recombination. Quantitative real-time PCR and northern blot analysis were used to study RNA transcript levels. Copper sensitivity of each mutant in vitro was determined using a plate assay. Results: Cuf1 is indispensable for C. neoformans survival in both high and low copper conditions. Cuf1 transcript levels do not change in response to copper, however genes that are up-regulated in high or low copper conditions are dependent on Cuf1 for proper transcriptional control. Conclusion: The Cuf1 transcriptional activator is responsible for copper homeostasis in the fungal pathogen C. neoformans. Future work will be focused on understanding what role copper plays during infection.


Subject Category: M. Mycology including clinical and basic studies of fungal infections

Richard Festa, Ph.D., Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC

Disclosures:

R. Festa, None

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