Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Candida albicans: A molecular revolution built on lessons from budding yeast

Candida albicans: A molecular revolution built on lessons from budding yeast The analysis of Candida albicans is complicated by the lack of a complete sexual cycle, which obviates classical genetic approaches, and by the use of an unconventional codon, which prohibits the use of heterologous genes. The availability of the C. albicans genome sequence (×10.4 coverage) has facilitated reverse-genetic and genomic approaches for investigating C. albicans biology. Transformation using a recyclable URA3 marker or PCR-mediated gene targeting with several recently available selectable markers and codon-optimized epitopes has improved the ability to generate genetically altered C. albicans strains. The C. albicans genome sequence has identified many Saccharomyces cerevisiae homologues, as well as many genes with no obvious homologue in S. cerevisiae. Genes that differ from S. cerevisiae might have an important role in virulence. C. albicans grows as yeast, pseudohyphae (elongated budded cells) or true hyphae (cells with parallel sides and no constriction at the site of septation). True hyphae are fundamentally different from pseudohyphae and yeast in the organization of the cell cycle. Morphogenesis is regulated by cell-cycle regulators, such as the major cyclin-dependent kinase Fkh2, which is a transcriptional regulator of B-cyclin expression, and Mad2, which is a spindle checkpoint protein. Although Mad2 is not required for growth in vitro it is important for virulence in mice, indicating that modulation of cell-cycle events might be especially important for C. albicans cells growing in a mammalian host. Different environmental conditions, such as high temperature, high pH and the presence of serum, induce yeast cells to form true hyphae. The cAMP and the mating-pheromone-response–MAP-kinase–signal-transduction pathways target transcription factors, such as Efg1 and Cph1, that promote morphogenesis. The Rim101 pathway responds to pH and the Czf1 pathway responds to the presence of solid matrix. Several partial-genome array studies, and recently reported whole-genome microarray studies, are uncovering genes the transcription of which changes on exposure to anti-fungal drugs or during the yeast-to-hyphal transition. C. albicans has mating-type-like (MTL) genes that resemble S. cerevisiae mating-type genes, and diploid cells that carry only one type of MTL gene can fuse with cells of the opposite mating type to form recombinant tetraploids. The mechanism by which diploids are regenerated is not known. Several systems of phenotypic switching — the epigenetic alteration of colony phenotypes — exist in Candida species. The best-studied phenotypic switching system is the switch between white and opaque colony morphology. The molecular and genomic tools are now in place to enable direct studies of C. albicans that will provide a deeper understanding of pathways and genes, including those that are important for pathogenesis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Reviews Genetics Springer Journals

Candida albicans: A molecular revolution built on lessons from budding yeast

Berman, Judith; Sudbery, Peter E.
Nature Reviews Genetics , Volume 3 (12) – Dec 1, 2002
Download PDF
13 pages

Loading next page...
 
/lp/springer-journals/candida-albicans-a-molecular-revolution-built-on-lessons-from-budding-fBi0I7zRkh

References (119)

Publisher
Springer Journals
Copyright
Copyright © 2002 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Human Genetics; Cancer Research; Agriculture; Gene Function; Animal Genetics and Genomics
ISSN
1471-0056
eISSN
1471-0064
DOI
10.1038/nrg948
Publisher site
See Article on Publisher Site

Abstract

The analysis of Candida albicans is complicated by the lack of a complete sexual cycle, which obviates classical genetic approaches, and by the use of an unconventional codon, which prohibits the use of heterologous genes. The availability of the C. albicans genome sequence (×10.4 coverage) has facilitated reverse-genetic and genomic approaches for investigating C. albicans biology. Transformation using a recyclable URA3 marker or PCR-mediated gene targeting with several recently available selectable markers and codon-optimized epitopes has improved the ability to generate genetically altered C. albicans strains. The C. albicans genome sequence has identified many Saccharomyces cerevisiae homologues, as well as many genes with no obvious homologue in S. cerevisiae. Genes that differ from S. cerevisiae might have an important role in virulence. C. albicans grows as yeast, pseudohyphae (elongated budded cells) or true hyphae (cells with parallel sides and no constriction at the site of septation). True hyphae are fundamentally different from pseudohyphae and yeast in the organization of the cell cycle. Morphogenesis is regulated by cell-cycle regulators, such as the major cyclin-dependent kinase Fkh2, which is a transcriptional regulator of B-cyclin expression, and Mad2, which is a spindle checkpoint protein. Although Mad2 is not required for growth in vitro it is important for virulence in mice, indicating that modulation of cell-cycle events might be especially important for C. albicans cells growing in a mammalian host. Different environmental conditions, such as high temperature, high pH and the presence of serum, induce yeast cells to form true hyphae. The cAMP and the mating-pheromone-response–MAP-kinase–signal-transduction pathways target transcription factors, such as Efg1 and Cph1, that promote morphogenesis. The Rim101 pathway responds to pH and the Czf1 pathway responds to the presence of solid matrix. Several partial-genome array studies, and recently reported whole-genome microarray studies, are uncovering genes the transcription of which changes on exposure to anti-fungal drugs or during the yeast-to-hyphal transition. C. albicans has mating-type-like (MTL) genes that resemble S. cerevisiae mating-type genes, and diploid cells that carry only one type of MTL gene can fuse with cells of the opposite mating type to form recombinant tetraploids. The mechanism by which diploids are regenerated is not known. Several systems of phenotypic switching — the epigenetic alteration of colony phenotypes — exist in Candida species. The best-studied phenotypic switching system is the switch between white and opaque colony morphology. The molecular and genomic tools are now in place to enable direct studies of C. albicans that will provide a deeper understanding of pathways and genes, including those that are important for pathogenesis.

Journal

Nature Reviews Genetics – Springer Journals

Published: Dec 1, 2002

There are no references for this article.