Title: 1.Temporal coordination of different signaling pathways during hyphal development in Candida albicans

2. Search for new anti-fungal drugs

Presenter: Haoping Liu; Richard Calderone

University: University of California; Georgetown University

Time: 9:00-12:00, July 16, 2012

Venue: Room A102, Institute of Microbiology, Chinese Academy of Sciences

Abstract:

Candida albicans is able to undergo reversible morphological changes between yeast and hyphal forms in response to environmental cues. This morphological plasticity is essential for its pathogenesis and survival in its hosts. Although manysignalingpathwaysare known to beimportant for hyphaldevelopment, how C. albicans coordinates information from different signaling pathways during hyphal regulation remains a major question. We show that hyphal development requires two temporally linked changes in promoter chromatin, which is sequentially regulated by temporarily clearing the transcription inhibitor Nrg1 upon activation of cAMP/PKA and promoter recruitment of the histone deacetylase Hda1 under reduced Tor1 signaling. The GATA family transcription factor Brg1 recruits Hda1 to promotersfor sustainedhyphal development and BRG1 expression is a sensitive readout of reduced Tor1 signaling. Using a forward genetic screen for mutants that can sustain hyphalelongation in rich media, we find that reduced Tor1 signaling lowers the basal activity of the Hog1 MAP kinase to sustain hyphal elongation. Our studies suggest that temporal coordination allows integration of information from various signaling pathways to controlhyphal development.—Haoping Liu

Fungal infections such as candidiasis and cryptococcosis are extremely common in HIV/AIDS patients. In fact, their frequency in many countries such as China exceeds that of tuberculosis. Also, hospital-acquired candidiasis is 3rd-4th in frequency in the USA and other countries. Current therapeutics can be toxic to patients, costly, and often result in resistance to the drug by these pathogens. So, new therapeutic compounds are needed. My laboratory focuses upon antifungal drug discovery. We use both a traditional approach which focuses upon screening libraries of potential inhibitory compounds, as well as genomic approaches. Thus far, we have 4 compounds in patent with good inhibitory activity and have identified 3 fungal-specific genes with important functions for the pathogens. Further development of these products is ongoing.—Richard  Calderone