Abstract
The extension of germ tubes into elongated hyphae by Candida albicans is essential for damage of host cells. The C. albicans-specific gene EED1 plays a crucial role in this extension and maintenance of filamentous growth. eed1Δ cells failed to extend germ tubes into long filaments and switched back to yeast growth after 3 h of incubation during growth on plastic surfaces. Expression of EED1 is regulated by the transcription factor Efg1 and ectopic overexpression of EED1 restored filamentation in efg1Δ. Transcriptional profiling of eed1Δ during infection of oral tissue revealed down-regulation of hyphal associated genes including UME6, encoding another key transcriptional factor. Ectopic overexpression of EED1 or UME6 rescued filamentation and damage potential in eed1Δ. Transcriptional profiling during overexpression of UME6 identified subsets of genes regulated by Eed1 or Ume6. These data suggest that Eed1 and Ume6 act in a pathway regulating maintenance of hyphal growth thereby repressing hyphal-to-yeast transition and permitting dissemination of C. albicans within epithelial tissues.
Highlights
Candida albicans is normally a harmless commensal and part of the microflora on mucosal surfaces, but frequently causes superficial infections such as oral or vaginal thrush
We suggest that Eed1 and Ume6 act in a pathway which controls the extension of germ tubes into hyphae, the hyphal-toyeast transition and escape from non-phagocytic host cells
EED1 is unique to C. albicans Using Blast searches within the available genomic sequences we aimed to identify homologues of EED1
Summary
Candida albicans is normally a harmless commensal and part of the microflora on mucosal surfaces, but frequently causes superficial infections such as oral or vaginal thrush. Infection of epithelial surfaces is associated with extensive growth, invasion into and dissemination within epithelial tissues and inflammation. For example after organ transplantation, the fungus may cause invasive and life threatening systemic infections. In these patients, the fungus can disseminate, usually from the gastrointestinal tract or from biofilms on medical devices, via the bloodstream leading to invasion of organs such as the liver or kidney [1]. After initial invasion into superficial epithelial cells, fungal hyphae can penetrate into deeper cell layers and disseminate, as shown previously for oral epithelial tissue [12]
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