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The antifungal plant defensin RsAFP2 isolated from radish interacts with fungal glucosylceramides and induces apoptosis in Candida albicans. To further unravel the mechanism of RsAFP2 antifungal action and tolerance mechanisms, we screened a library of 2868 heterozygous C. albicans deletion mutants and identified 30 RsAFP2-hypersensitive mutants. The most(More)
Starting with the discovery of penicillin, the pharmaceutical industry has relied extensively on natural products (NPs) as an unparalleled source of bioactive small molecules suitable for antibiotic development. However, the discovery of structurally novel and chemically tractable NPs with suitable pharmacological properties as antibiotic leads has waned in(More)
Candida albicans is a prevalent fungal pathogen amongst the immunocompromised population, causing both superficial and life-threatening infections. Since C. albicans is diploid, classical transmission genetics can not be performed to study specific aspects of its biology and pathogenesis. Here, we exploit the diploid status of C. albicans by constructing a(More)
One potentially rich source of possible targets for antifungal therapy are those Candida albicans genes deemed essential for growth under the standard culture (i.e., in vitro) conditions; however, these genes are largely unexplored as drug targets because essential genes are not experimentally amenable to conventional gene deletion and virulence studies.(More)
The balance between saturated and unsaturated fatty acids plays a crucial role in determining the membrane fluidity. In the diploid fungal pathogen Candida albicans, the gene for fatty acid Delta9 desaturase, OLE1, is essential for viability. Using a reverse genetic approach, termed the fitness test, we identified a group of structurally related synthetic(More)
Natural products provide an unparalleled source of chemical scaffolds with diverse biological activities and have profoundly impacted antimicrobial drug discovery. To further explore the full potential of their chemical diversity, we survey natural products for antifungal, target-specific inhibitors by using a chemical-genetic approach adapted to the human(More)
Mechanism-of-action (MOA) studies of bioactive compounds are fundamental to drug discovery. However, in vitro studies alone may not recapitulate a compound's MOA in whole cells. Here, we apply a chemogenomics approach in Candida albicans to evaluate compounds affecting purine metabolism. They include the IMP dehydrogenase inhibitors mycophenolic acid and(More)
Candida albicans is the principal human fungal pathogen that leads to life-threatening mycoses worldwide. To study its pathobiology, we characterized genes for two enzymes involved in the de novo purine biosynthesis pathway: ADE8 (encoding phosphoribosylglycinamide formyl-transferase) and GUA1 (GMP synthase). Heterozygous and homozygous disruption strains(More)
BACKGROUND Primary cardiac sarcomas are rare diseases with a poor prognosis. This study aims to provide a prognostic analysis after different levels of resections of cardiac sarcomas. METHODS Twenty-nine patients undergoing resections of primary cardiac sarcomas at the Zhongshan Hospital from September 1995 to July 2012 were retrospectively reviewed. (More)