Effects of copper homeostasis on growth morphology and genome wide expression in the fungal pathogen Cryptococcus neoformans.
Ellis, Shannon*, Brittany Kujat, David Portonova, Michael Portonova and Jeramia Ory.

Cryptococcus neoformans is an opportunistic fungal pathogen found in soil and avian feces that infects primarily immunocompromised individuals. Recent studies have indicated that the copper import pathway of C. neoformans plays an important role in the pathogenicity of the organism. The copper sensing transcription factor Cuf1p is a major regulator of the copper import pathway, and is homologous to other metal-sensitive transcription factors found in S.cereviscae and S.pombe. Cuf1p's primary role is to upregulate copper transporters in response to copper starvation conditions. Our results demonstrate that a _cuf1 strain of C.neoformans is unable to grow in copper depleted environments as expected. However, the aberrant growth phenotype of _cuf1 is restored to near wild type levels by the addition of extraneous copper or iron. This suggests that _cuf1's slow growth reflects the inability of a copper starved cell to import iron rather than a nutritional need for copper. Unexpectedly, _cuf1 is also more sensitive to high concentrations of copper, suggesting it may play a role in regulating both copper starvation and copper toxicity responses. To map the regulatory network controlled by Cuf1p, we have begun microarray analysis of whole genome expression of wild-type C.neoformans in varying concentrations of copper.