Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity
By S. Noble, S. French, L. Kohn, V. Chen, Alexander Johnson. Nature Genetics, 2010
661 citations recorded by the source corpus.
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.
View Paper: https://www.semanticscholar.org/paper/e79be297a418b32cebdf0cdbf93e9d622827465b
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Citations in the corpus
- Phenotypic Landscape of a Bacterial Cell (2010, unknown): “Singlegene deletion ordered libraries are currently available for only a handful of organisms (Cameron et al., 2008; de Berardinis et al., 2008; Gallagher et al., 2007; Goodman et al., 2009; Kim et al., 2010; Liu et al., 2008; Noble et al., 2010; references in Barker et al., 2010), but advances in t”
- A Recently Evolved Transcriptional Network Controls Biofilm Development in Candida albicans (2012, methodology): “The transcription regulator mutant strains were made Arg+ by transforming with PmeI-digested pSN105 (Noble et al., 2010) to yield strains CJN2302 (efg1D/D), CJN2330 (tec1D/D), CJN2334 (bcr1D/D), CJN2338 (brg1D/D), CJN2408 (rob1D/D), and CJN2412 (ndt80D/D).”
- Modes of antifungal action and in planta functions of plant defensins and defensin-like peptides (2013, background): “, 2004), and was recently shown to be required for virulence in Candida albicans (Noble et al., 2010).”