Haploinsufficiency-based large-scale forward genetic analysis of filamentous growth in the diploid human fungal pathogen C.albicans
Open accessAbstract
Candida albicans is the most prevalent human fungal pathogen. Here, we take advantage of haploinsufficiency and transposon mutagenesis to perform large-scale loss-of-function genetic screen in this organism. We identified mutations in 146 genes that affect the switch between its single-cell (yeast) form and filamentous forms of growth; this switch appears central to the virulence of C.albicans. The encoded proteins include those involved in nutrient sensing, signal transduction, transcriptional control, cytoskeletal organization and cell wall construction. Approximately one-third of the genes identified in the screen lack homologs in Saccharomyces cerevisiae and other model organisms and thus constitute candidate antifungal drug targets. These results illustrate the value of performing forward genetic studies in bona fide pathogens.
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Seven members of the FGR genes, involved in filamentous growth and specifically expanded in C. albicans, are among the 240 genes.
“In addition, seven members of the FGR genes (Uhl et al., 2003), involved in filamentous growth and specifically expanded in C. albicans (Butler et al., 2009), are also among the 240 genes”
From The evolution of drug resistance in clinical isolates of Candida albicans. (2015) · cites this paper as Uhl et al., 2003
The evolved isolate 4617 in patient 59 had a dramatic increase in filamentation relative to the progenitor, concomitant with the appearance of persistent SNPs in genes associated with filamentous growth: CHO1, MNN2, and 7 different FGR genes.
“For example, the evolved isolate 4617 in patient 59 had a dramatic increase in filamentation relative to the progenitor, which was concomitant with the appearance of persistent SNPs in genes associated with filamentous growth: CHO1, MNN2, and 7 different FGR (filamentous growth regulator) genes (Uhl et al., 2003).”
From The evolution of drug resistance in clinical isolates of Candida albicans. (2015) · cites this paper as Uhl et al., 2003
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- Authors
- Uhl, M. A., Biery, M., Craig, N., & Johnson, A. D.
- Affiliations
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Johnson, Alexander D.
- Venue
- The EMBO Journal
- Published
- 2003-06-01
- Volume
- 22
- Issue
- 11
- Pages
- 2668-2678
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC156753
- OpenAlex
- W2167798305
- Cited by
- 191
- References
- 59
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 4 · 2020: 10 · 2019: 4 · 2018: 15 · 2017: 6 · 2016: 8 · 2015: 9 · 2014: 17 · 2013: 10 · 2012: 9
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Damon Runyon Cancer Research Foundation
- National Institutes of Health
- Stanford Bio-X
- National Institute of General Medical Sciences (GM37049, R01GM037049)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida albicans, haploinsufficiency, forward genetic screen, filamentous growth, yeast-to-hypha transition, transposon mutagenesis, loss-of-function mutations, fungal virulence, antifungal drug targets, nutrient sensing, signal transduction, transcriptional regulation, cytoskeletal organization, cell wall biosynthesis
- MeSH terms
- Candida albicans, Genes, Fungal, Genetic Techniques, Humans, Phenotype, Saccharomyces cerevisiae, Virulence, Mutagenesis, Insertional
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