Some biological features of Candida albicans mutants for genes coding fungal proteins containing the CFEM domain

Perez, Ana; Ramage, Gordon; Blanes, Rosario; Murgui, Amelia; Casanova, Manuel; Martinez, Josè

doi:10.1111/j.1567-1364.2010.00714.x

Cited by 40 publications

(35 citation statements)

References 63 publications

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“…Csa1 localizes in the hyphal wall (67,71) and was previously shown to be upregulated by Bcr1 (20). Consistent with our results, Perez et al (72,73) showed a decrease in the thickness of biofilms formed by an a/␣ CSA1 deletion mutant. Although Csa2 does not contain a GPI anchor, it has been shown to be an extracellular protein (74).…”

Section: Discussionsupporting

confidence: 81%

Identification of Genes Upregulated by the Transcription Factor Bcr1 That Are Involved in Impermeability, Impenetrability, and Drug Resistance of Candida albicans a/ α Biofilms

et al. 2013

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Candida albicans forms two types of biofilm, depending upon the configuration of the mating type locus. Although architecturally similar, a/␣ biofilms are impermeable, impenetrable, and drug resistant, whereas a/a and ␣/␣ biofilms lack these traits. The difference appears to be the result of an alternative matrix. Overexpression in a/a cells of BCR1, a master regulator of the a/␣ matrix, conferred impermeability, impenetrability, and drug resistance to a/a biofilms. Deletion of BCR1 in a/␣ cells resulted in the loss of these a/␣-specific biofilm traits. Using BCR1 overexpression in a/a cells, we screened 107 genes of interest and identified 8 that were upregulated by Bcr1. When each was overexpressed in a/a biofilms, the three a/␣ traits were partially conferred, and when each was deleted in a/␣ cells, the traits were partially lost. Five of the eight genes have been implicated in iron homeostasis, and six encode proteins that are either in the wall or plasma membrane or secreted. All six possess sites for O-linked and N-linked glycosylation that, like glycosylphosphatidylinositol (GPI) anchors, can cross-link to the wall and matrix, suggesting that they may exert a structural role in conferring impermeability, impenetrability, and drug resistance, in addition to their physiological functions. The fact that in a screen of 107 genes, all 8 of the Bcr1-upregulated genes identified play a role in impermeability, impenetrability, and drug resistance suggests that the formation of the a/␣ matrix is highly complex and involves a larger number of genes than the initial ones identified here.

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Section: Discussionsupporting

confidence: 81%

Identification of Genes Upregulated by the Transcription Factor Bcr1 That Are Involved in Impermeability, Impenetrability, and Drug Resistance of Candida albicans a/ α Biofilms

et al. 2013

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“…In some species (such as the plant pathogen Magnaporthe grisea), CFEM members are involved in pathogenesis (47). In C. albicans, the CFEM family is associated with adhesion and biofilm formation (62) and in acquisition of iron from heme (82,83). Levels of Pga10 and Rbt5 in the cell wall are increased when oxygen is limited (72).…”

Section: Discussionmentioning

confidence: 99%

“…We also observed significant increases in expression of three related cell wall genes (RBT5, PGA7, and PGA10) (see Table S2 in the supplemental material). These each contain an 8-cysteine domain, belong to the family CFEM (common in several fungal extracellular membranes), and are associated with biofilm development and heme binding (62,82).…”

Section: Induction Of Gene Expression By Hypoxiamentioning

confidence: 99%

Regulation of the Hypoxic Response in Candida albicans

et al. 2010

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The regulation of the response of Candida albicans to hypoxic (low-oxygen) conditions is poorly understood. We used microarray and other transcriptional analyses to investigate the role of the Upc2 and Bcr1 transcription factors in controlling expression of genes involved in cell wall metabolism, ergosterol synthesis, and glycolysis during adaptation to hypoxia. Hypoxic induction of the ergosterol pathway is mimicked by treatment with sterol-lowering drugs (ketoconazole) and requires UPC2. Expression of three members of the family CFEM (common in several fungal extracellular membranes) of cell wall genes (RBT5, PGA7, and PGA10) is also induced by hypoxia and ketoconazole and requires both UPC2 and BCR1. Expression of glycolytic genes is induced by hypoxia but not by treatment with sterol-lowering drugs, whereas expression of respiratory pathway genes is repressed. However, Upc2 does not play a major role in regulating expression of genes required for central carbon metabolism. Our results indicate that regulation of gene expression in response to hypoxia in C. albicans is complex and is signaled both via lowered sterol levels and other unstudied mechanisms. We also show that induction of filamentation under hypoxic conditions requires the Ras1-and Cdc35-dependent pathway.The human fungal pathogen Candida albicans grows on superficial and internal sites in the infected host, areas that differ significantly in the availability of oxygen (26). Under low-oxygen (hypoxic) conditions, C. albicans switches from yeast to hyphal growth, a phenotypic change that has been associated with invasion and virulence (24,30,54). Exposure to hypoxia results in increased expression of genes involved in ergosterol synthesis and glycolysis and reduced expression of oxidative phosphorylation (3, 69). There is also an increase in expression of some cell wall and hyphal-specific genes (69), which is reflected in changes in the cell wall proteome (72).Although the response to hypoxia has been well studied in fungi such as Saccharomyces cerevisiae and Schizosaccharomyces pombe, much less is known about the response in C. albicans. In S. pombe, a decrease in oxygen is detected by the reduction in sterol synthesis, which requires 12 molecules of oxygen to convert one squalene to ergosterol (38). Sterol content is sensed by Sre1 and Scp1, which are homologs of the human sterol regulatory element binding protein (SREBP) and Scap (SREBP cleavage-activating protein) (38, 77). Sre1 and Scp1 are localized in the membrane, where they remain when sterol and oxygen levels are high. When sterol levels drop, the N terminus of Sre1 is cleaved off, and it enters the nucleus, where it acts as a transcriptional regulator. Sre1 is the major regulator of the hypoxic response in S. pombe and regulates expression of Ͼ100 genes (38). It also functions in a sterol-independent manner (39). SREBPs are also important for sensing oxygen levels in the pathogenic fungi Cryptococcus neoformans and Aspergillus fumigatus (7,13,85).There are no obvious SREBP orthologs in...

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“…Cells grown at 42°C for 18 h showed a severe cell separation defect. Similarly, cell aggregates were also described for several mutants that show a defective wall, like the glycosylation mutant mnn9, pmt1, and pmt4 strains, the wall protein ecm33, pga10, and pga13 mutants, and the wall-associated transglycosylase bgl2 mutants (48,(63)(64)(65)(66). Gregori et al assigned the cell separation defect in caspofungin-treated cells to an increased expression of adhesins, mainly Als1 (67).…”

Section: Discussionmentioning

confidence: 99%

Surface Stress Induces a Conserved Cell Wall Stress Response in the Pathogenic Fungus Candida albicans

et al. 2013

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cThe human fungal pathogen Candida albicans can grow at temperatures of up to 45°C. Here, we show that at 42°C substantially less biomass was formed than at 37°C. The cells also became more sensitive to wall-perturbing compounds, and the wall chitin levels increased, changes that are indicative of wall stress. Quantitative mass spectrometry of the wall proteome using 15 N metabolically labeled wall proteins as internal standards revealed that at 42°C the levels of the ␤-glucan transglycosylases Phr1 and Phr2, the predicted chitin transglycosylases Crh11 and Utr2, and the wall maintenance protein Ecm33 increased. Consistent with our previous results for fluconazole stress, this suggests that a wall-remodeling response is mounted to relieve wall stress. Thermal stress as well as different wall and membrane stressors led to an increased phosphorylation of the mitogen-activated protein (MAP) kinase Mkc1, suggesting activation of the cell wall integrity (CWI) pathway. Furthermore, all wall and membrane stresses tested resulted in diminished cell separation. This was accompanied by decreased secretion of the major chitinase Cht3 and the endoglucanase Eng1 into the medium. Consistent with this, cht3 cells showed a similar phenotype. When treated with exogenous chitinase, cell clusters both from stressed cells and mutant strains were dispersed, underlining the importance of Cht3 for cell separation. We propose that surface stresses lead to a conserved cell wall remodeling response that is mainly governed by Mkc1 and is characterized by chitin reinforcement of the wall and the expression of remedial wall remodeling enzymes.

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Some biological features of Candida albicans mutants for genes coding fungal proteins containing the CFEM domain

Cited by 40 publications

References 63 publications

Identification of Genes Upregulated by the Transcription Factor Bcr1 That Are Involved in Impermeability, Impenetrability, and Drug Resistance of Candida albicans a/ α Biofilms

Identification of Genes Upregulated by the Transcription Factor Bcr1 That Are Involved in Impermeability, Impenetrability, and Drug Resistance of Candida albicans a/ α Biofilms

Regulation of the Hypoxic Response in Candida albicans

Surface Stress Induces a Conserved Cell Wall Stress Response in the Pathogenic Fungus Candida albicans

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