Journal
CELL HOST & MICROBE
Volume 9, Issue 3, Pages 243-251Publisher
CELL PRESS
DOI: 10.1016/j.chom.2011.02.003
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Funding
- National Institute of Allergy and Infectious Disease (NIAID) [R01AI065519, 5T32AI060537-07]
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The antiphagocytic polysaccharide capsule of the human fungal pathogen Cryptococcus neoformans is a major virulence attribute. However, previous studies of the pleiotropic virulence determinant Gat201, a GATA family transcription factor, suggested that capsule-independent antiphagocytic mechanisms exist. We have determined that Gat201 controls the mRNA levels of similar to 1100 genes (16% of the genome) and binds the upstream regions of similar to 130 genes. Seven Gat201-bound genes encode for putative and known transcription factors-including two previously implicated in virulence-suggesting an extensive regulatory network. Systematic analysis pinpointed two critical Gat201-bound genes, GAT204 (a transcription factor) and BLP1, which account for much of the capsule-independent antiphagocytic function of Gat201. A strong correlation was observed between the quantitative effects of single and double mutants on phagocytosis in vitro and on host colonization in vivo. This genetic dissection provides evidence that capsule-independent antiphagocytic mechanisms are pivotal for successful mammalian infection by C. neoformans.
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