Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity
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Open Access
- 13 June 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 42 (7), 590-598
- https://doi.org/10.1038/ng.605
Abstract
Suzanne Noble and colleagues present a library of ∼3,000 homozygous gene deletion strains of Candida albicans. The authors screened for infectivity in a mouse model and for yeast-to-hypha morphological switching. They identified 115 infectivity-attenuated mutants, half of which demonstrated normal morphological switching. Candida albicans is the most common cause of serious fungal disease in humans. Creation of isogenic null mutants of this diploid organism, which requires sequential gene targeting, allows dissection of virulence mechanisms. Published analyses of such mutants show a near-perfect correlation between C. albicans pathogenicity and the ability to undergo a yeast-to-hypha morphological switch in vitro. However, most studies have used mutants constructed with a marker that is itself a virulence determinant and therefore complicates their interpretation. Using alternative markers, we created ∼3,000 homozygous deletion strains affecting 674 genes, or roughly 11% of the C. albicans genome. Screening for infectivity in a mouse model and for morphological switching and cell proliferation in vitro, we identified 115 infectivity-attenuated mutants, of which nearly half demonstrated normal morphological switching and proliferation. Analysis of such mutants revealed that virulence requires the glycolipid glucosylceramide. To our knowledge, this is the first C. albicans small molecule that has been found to be required specifically for virulence.Keywords
This publication has 58 references indexed in Scilit:
- Widespread occurrence of chromosomal aneuploidy following the routine production ofCandida albicansmutantsFEMS Yeast Research, 2009
- New tools at the Candida Genome Database: biochemical pathways and full-text literature searchNucleic Acids Research, 2009
- Aneuploid Chromosomes Are Highly Unstable during DNA Transformation of Candida albicansEukaryotic Cell, 2009
- An RNA Transport System in Candida albicans Regulates Hyphal Morphology and Invasive GrowthPLoS Genetics, 2009
- Trimorphic stepping stones pave the way to fungal virulenceProceedings of the National Academy of Sciences of the United States of America, 2009
- The Candida albicans phosphatase Inp51p interacts with the EH domain protein Irs4p, regulates phosphatidylinositol-4,5-bisphosphate levels and influences hyphal formation, the cell integrity pathway and virulenceMicrobiology, 2008
- Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicansGenome Research, 2007
- Inhibition of Filamentation Can Be Used To Treat Disseminated CandidiasisAntimicrobial Agents and Chemotherapy, 2006
- Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformansJCI Insight, 2006
- Glucosylceramide Synthases, a Gene Family Responsible for the Biosynthesis of Glucosphingolipids in Animals, Plants, and FungiOnline Journal of Public Health Informatics, 2001