In 2010, we initiated the construction of an insertional mutant library by the Agrobacterium mediated transformation of Cryptococcus gattii and isolated 30,000 mutant clones by the summer of 2011. This library will serve as a tool for identification of the genes that are involved in the manifestation of the pathobiological differences between the two species. During 2011-2012, we compared the pattern of nitrogen assimilation between C. gattii and C. neoformans and found striking differences in the utilization of D-amino acids such as D-proline and D-alanine. Furthermore, we discovered that the primary target organ for the two species in mice is different: the primary target organ for C. neoformans is the brain while for C. gattii, it is the lung. Since the host response toward the two species is clearly different, we initiated a study to compare the host-paracite relationship between the two species in 2013. Using the plasma samples from immunocompetent patients with cryptococcal menigitis in China and Australia, we found the presence of anti-GM-CSF autoantibodies in plasma to be a risk factor for C. gattii infection and not for C. neoformans infection.

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Samarasinghe, Himeshi; Aceituno-Caicedo, David; Cogliati, Massimo et al. (2018) Genetic Factors and Genotype-Environment Interactions Contribute to Variation in Melanin Production in the Fungal Pathogen Cryptococcus neoformans. Sci Rep 8:9824
Ferreira-Paim, Kennio; Andrade-Silva, Leonardo; Fonseca, Fernanda M et al. (2017) MLST-Based Population Genetic Analysis in a Global Context Reveals Clonality amongst Cryptococcus neoformans var. grubii VNI Isolates from HIV Patients in Southeastern Brazil. PLoS Negl Trop Dis 11:e0005223
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Chang, Yun C; Khanal Lamichhane, Ami; Bradley, James et al. (2015) Differences between Cryptococcus neoformans and Cryptococcus gattii in the Molecular Mechanisms Governing Utilization of D-Amino Acids as the Sole Nitrogen Source. PLoS One 10:e0131865
Saijo, Tomomi; Chen, Jianghan; Chen, Sharon C-A et al. (2014) Anti-granulocyte-macrophage colony-stimulating factor autoantibodies are a risk factor for central nervous system infection by Cryptococcus gattii in otherwise immunocompetent patients. MBio 5:e00912-14
Ngamskulrungroj, Popchai; Chang, Yun; Sionov, Edward et al. (2012) The primary target organ of Cryptococcus gattii is different from that of Cryptococcus neoformans in a murine model. MBio 3:

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