A major role for capsule-independent phagocytosis-inhibitory mechanisms in mammalian infection by Cryptococcus neoformans.
Cell Host Microbe, 2011/3/17;9(3):243-251.
Chun CD[1], Brown JCS[1], Madhani HD[2]
Affiliations
PMID: 21402362DOI: 10.1016/j.chom.2011.02.003
Impact factor: 31.316
Abstract
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 ∼1100 genes (16% of the genome) and binds the upstream regions of ∼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.
MeSH terms
Animals; Bacterial Capsules; Chromatin Immunoprecipitation; Cryptococcosis; Cryptococcus neoformans; Fungal Proteins; GATA Transcription Factors; Gene Expression Profiling; Gene Expression Regulation, Fungal; Host-Pathogen Interactions; Humans; Lung; Mice; Oligonucleotide Array Sequence Analysis; Phagocytosis; Transcriptional Activation; Virulence Factors
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