Isolation of the Candida albicans homologs of Saccharomyces cerevisiae KRE6 and SKN1: expression and physiological function

  title={Isolation of the Candida albicans homologs of Saccharomyces cerevisiae KRE6 and SKN1: expression and physiological function},
  author={Toshiyuki Mio and Toshiko Yamada-Okabe and Tomio Yabe and Tasuku Nakajima and Mikio Arisawa and Hisafumi Yamada‐Okabe},
  journal={Journal of Bacteriology},
  pages={2363 - 2372}
Cell wall beta-glucan in a pathogenic fungus, Candida albicans, is highly branched with beta-1,3 and beta-1,6 linkages. We have isolated the C. albicans cDNAs for KRE6 and SKN1, the genes required for beta-1,6-glucan synthesis in Saccharomyces cerevisiae. The results of Northern blot analysis revealed that C. albicans KRE6 was expressed at a higher level than SKN1 in the yeast phase, while SKN1 expression was strongly induced upon induction of hyphal formation. In addition, the C. albicans KRE6… 

Deletion of the CaBIG1 Gene Reduces β-1,6-Glucan Synthesis, Filamentation, Adhesion, and Virulence in Candida albicans

The results indicate that adhesion failure and morphological abnormality contribute to the attenuated virulence of the Cabig1Δ mutant, which showed markedly attenuates virulence in a mouse model of systemic candidiasis.

KRE5 Gene Null Mutant Strains of Candida albicans Are Avirulent and Have Altered Cell Wall Composition and Hypha Formation Properties

Saccharomyces cerevisiae is the only eukaryotic organism so far described lacking UGGT-mediated transient reglucosylation of N-linked oligosaccharides, and deletion of both alleles of the Candida albicans KRE5 gene gives rise to viable cells that are larger than those of the wild type (WT), tend to aggregate, have enlarged vacuoles, and show major cell wall defects.

Isolation of Candida glabrata Homologs of the Saccharomyces cerevisiae KRE9 and KNH1Genes and Their Involvement in Cell Wall β-1,6-Glucan Synthesis

Although a cgknh1Delta mutant showed no phenotype beyond slightly increased sensitivity to the K1 killer toxin, disruption of CgKRE9 resulted in several phenotypes similar to those of the S. cerevisiae kre9Delta null mutant, and cgkre9 Delta cells were shown to be sensitive to calcofluor white specifically on glucose medium.

The Candida albicans KRE9 gene is required for cell wall beta-1, 6-glucan synthesis and is essential for growth on glucose.

Disruption of the CaKRE9 gene in C. albicans shows that CaKre9p is required for the synthesis or assembly of this fungal polymer, and the gene product is a potentially useful candidate as a target for fungal-specific drugs.

PHR1, a pH-regulated gene of Candida albicans encoding a glucan-remodelling enzyme, is required for adhesion and invasion.

Results suggest that PHR1 is not required for the induction of hyphal development but plays a key role in the maintenance of hypha growth, and the beta-(1,3)-glucan processing catalysed by Phr1p is of fundamental importance in thetenance of the morphological state on which the adhesive and invasive properties of C. albicans greatly depend.

Regulated overexpression of CDR1 in Candida albicans confers multidrug resistance.

Overexpression of Cdr1p in C. albicans FL3 conferred resistance to structurally unrelated chemicals such as terbinafine, brefeldin A, cerulenin and nigericin as well as to azole antifungal agents, but not resistance to polyene antibiotics.

Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-D-glucan synthase inhibitors

It is concluded that C. albicans strains CAI4R1, NR2, and NR4 are heterozygous for a dominant or semidominant pneumocandin resistance mutation at CaFKS1, and CaFks1p is a target of the echinocandins.

Regulation of the Candida albicans cell wall damage response by transcription factor Sko1 and PAS kinase Psk1.

Results show that protein kinase Psk1 is required for expression of SKO1 and of Sko1-dependent genes in response to caspofungin, and lies in a newly described signal transduction pathway.

The role of the Candida albicans histidine kinase [CHK1) gene in the regulation of cell wall mannan and glucan biosynthesis.

Analyzing glucan, mannan and chitin profiles in strains deleted in chk1 compared to a gene-reconstituted strain (CHK23) and a parental strain CAF2 identified a new function for a histidine kinase two-component signal protein in a human pathogenic fungus.

Cloning of the Candida albicans homolog of Saccharomyces cerevisiae GSC1/FKS1 and its involvement in beta-1,3-glucan synthesis

Results demonstrate that C. albicans GSC1 is the gene for a subunit of beta-1,3-glucan synthase.



Isolation from Candida albicans of a functional homolog of the Saccharomyces cerevisiae KRE1 gene, which is involved in cell wall beta-glucan synthesis

Structural and functional similarities imply that the canKRE1 gene carries out a function in C. albicans cell wall assembly similar to that observed in S. cerevisiae, which results in resistance to K1 killer toxin.

Attenuated virulence of chitin-deficient mutants of Candida albicans.

Despite their relatively normal growth, chitin-deficient mutants are significantly less virulent than the parental strain in both immunocompetent and immunosuppressed mice, suggesting that the reduced virulence of the mutants is not due to accelerated clearing.

Characterization of the yeast (1-->6)-beta-glucan biosynthetic components, Kre6p and Skn1p, and genetic interactions between the PKC1 pathway and extracellular matrix assembly

KRE6 and SKN1 are predicted to encode homologous proteins that participate in assembly of the cell wall polymer (1-->6)-beta-glucan, and both Kre6p and Skn1p possess COOH-terminal domains with significant sequence similarity to two recently identified glucan-binding proteins.

The Yeast KRE9 Gene Encodes an 0 Glycoprotein Involved in Cell Surface ,-Glucan Assembly

Double mutants were generated by crossing kre9A strains with strains harboring a null mutation in the KREI, KRE6, or KREII gene, and each of these double mutants was found to be inviable in the SEY6210 background.

SKN1 and KRE6 define a pair of functional homologs encoding putative membrane proteins involved in beta-glucan synthesis

Since single disruptions of these genes lead to structurally wild-type (1-->6)-beta-glucan polymers, Kre6p and Skn1p appear to function independently, possibly in parallel, in (1 -->6)- beta-glUCan biosynthesis.

Cloning of the Saccharomyces cerevisiae gene whose overexpression overcomes the effects of HM-1 killer toxin, which inhibits beta-glucan synthesis

Overexpression of the truncated HKR1 encoding the C-terminal half of Hkr1p made the cells more resistant to HM-1 killer toxin than the full-length H KR1 did, demonstrating that the C -terminalhalf of HKR 1p is essential for overcoming the effect of HM- 1 killer toxin.

Yeast beta-glucan synthesis: KRE6 encodes a predicted type II membrane protein required for glucan synthesis in vivo and for glucan synthase activity in vitro.

  • T. RoemerH. Bussey
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1991
The phenotype and structure of the KRE6 product, Kre 6p, suggest that Kre6p may be a beta-glucan synthase, and if so, it implies that beta- glucan syntheses are functionally redundant in yeast.

Characterization and gene cloning of 1,3-beta-D-glucan synthase from Saccharomyces cerevisiae.

1,3-beta-D-Glucan synthase of Saccharomyces cerevisiae was solubilized and purified up to 700-fold by product entrapment and disruption of each gene was not lethal, but disruption of both genes was lethal.

The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1,3-beta-D-glucan synthase.

Results suggest that FKS1 encodes a subunit of 1,3-beta-D-glucan synthase, consistent with previous observations that the etg1-1 mutation results in echinocandin-resistant glucan synth enzyme activity associated with the nonextractable membrane fraction of the enzyme.

SKN7, a yeast multicopy suppressor of a mutation affecting cell wall beta-glucan assembly, encodes a product with domains homologous to prokaryotic two-component regulators and to heat shock transcription factors

A search for genes which could suppress the growth defect in a strain disrupted at the KRE9 locus has identified the SKN7 gene, which is predicted to encode a 70-kDa protein, Skn7p, with a region of homology to the DNA binding domain of the Saccharomyces cerevisiae heat shock transcription factor, Hsf1p.