Gene regulation and host adaptation mechanisms in Candida albicans

Staib, Peter; Wirsching, Stephanie; Strauß, Anja; Morschhäuser, Joachim

doi:10.1078/1438-4221-00114

Cited by 21 publications

(17 citation statements)

References 48 publications

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“…It is not possible to discern from our data whether the attenuated virulence is a consequence of impaired DNA damage responses, dysregulated morphogenesis, some other process, or a combination of mechanisms. In general, it is unclear whether morphogenesis per se contributes to the pathogenesis of candidiasis rather than morphology-associated patterns of gene expression (24,46,48). In fact, pathways regulating C. albicans morphogenesis converge to influence the expression of genes encoding diverse virulence factors (29,32).…”

Section: Discussionmentioning

confidence: 99%

Candida albicans RFX2 Encodes a DNA Binding Protein Involved in DNA Damage Responses, Morphogenesis, and Virulence

et al. 2009

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We previously showed that Candida albicans orf19.4590, which we have renamed RFX2, expresses a protein that is reactive with antibodies in persons with candidiasis. In this study, we demonstrate that C. albicans RFX2 shares some functional redundancy with Saccharomyces cerevisiae RFX1. Complementation of an S. cerevisiae rfx1 mutant with C. albicans RFX2 partially restored UV susceptibility and the repression of DNA damage response genes. DNA damage-and UV-induced genes RAD6 and DDR48 were derepressed in a C. albicans rfx2 null mutant strain under basal conditions, and the mutant was significantly more resistant to UV irradiation, heat shock, and ethanol than wild-type strain SC5314. The rfx2 mutant was hyperfilamentous on solid media and constitutively expressed hypha-specific genes HWP1, ALS3, HYR1, ECE1, and CEK1. The mutant also demonstrated increased invasion of solid agar and significantly increased adherence to human buccal epithelial cells. During hematogenously disseminated candidiasis, mice infected with the mutant had a significantly delayed time to death compared to the wild type. During oropharyngeal candidiasis, mice infected with the mutant had significantly lower tissue burdens in the oral cavity and esophagus at 7 days and they were less likely to develop disseminated infections because of mucosal translocation. The data demonstrate that C. albicans Rfx2p regulates DNA damage responses, morphogenesis, and virulence.

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Section: Discussionmentioning

confidence: 99%

Candida albicans RFX2 Encodes a DNA Binding Protein Involved in DNA Damage Responses, Morphogenesis, and Virulence

et al. 2009

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“…PS has been demonstrated and described for pathogenic yeasts, including C. albicans (3,12,15,16,19,20,21,23,25,26), Candida glabrata (2, 10, 22), T. asahii (9), and C. neoformans (7). As a manifestation of apparent developmental programming, PS confers phenotypic variability and environmental adaptation that facilitates the survival and/or pathogenic success of the organism.…”

Section: Discussionmentioning

confidence: 99%

“…Phenotypic switching is an attractive explanation for such phenotypic variations in C. lusitaniae, since switching has been documented for other pathogenic yeasts, including Candida albicans (3,12,15,16,19,20,21,23,25,26), Candida glabrata (2,10,22), Trichosporon asahii (9), and Cryptococcus neoformans (7). This mechanism permits an organism to adapt to environmental changes through selective gene expression, including changes in the fungal response to antifungal agents.…”

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confidence: 99%

Phenotypic Switching in Candida lusitaniae on Copper Sulfate Indicator Agar: Association with Amphotericin B Resistance and Filamentation

2006

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Candida lusitaniae is an opportunistic yeast pathogen that has the ability to develop resistance to amphotericin B (AmB). The mechanism(s) for this resistance is not well understood, although there are data supporting mutations in sterol pathways and other data supporting phenotypic switching (PS). The goal of this study was to determine whether C. lusitaniae has a PS system and to characterize any phenotypes, including any changes in AmB MICs. When 10 4 CFU of an AmB-resistant (MIC of 16 to 32 g/ml) clinical strain was plated on yeast-peptone-dextrose (YPD) agar with 1 mM CuSO 4 , three colony colors were observed: light brown (LB) Ͼ Ͼ dark brown (DB) > white (W), similar to the result for Candida glabrata. Switching did occur with high AmB resistance (MIC of 256 g/ml) being associated with W, whereas LB and DB colonies had MICs of 2 to 8 g/ml and 2 to 16 g/ml, respectively. Filamentation (pseudohyphae) was associated with DB colonies. All phenotypes occurred spontaneously with greater frequency (ϳ10 ؊2 to 10 ؊4 ) than spontaneous mutations, and all phenotypes were reversible, fulfilling the two PS criteria. High AmB MICs were always associated with W colonies but not with all W colonies. Detection of PS on YPD-CuSO 4 is also similar to that in Candida glabrata, and we hypothesize that this is due to similarities in metallothionein gene expression. Phenotypic switching represents a key strategy in C. lusitaniae that confers a selective advantage during environmental challenges, including the ability to switch to AmB resistance.

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“…Lan et al found a relationship between phenotypic variation and metabolic flexibility in the genus Candida, which increases its selection according to the availability of nutrients in certain body regions (28). Phenotypic and genotypic variability such as the atypical Tween assimilation pattern in the case of M. furfur may, like the variability in Candida spp., be a determining factor in the infection strategy used by the microorganism, which in turn could be related to the expression of genes involved in pathogenic processes and colonization (39).…”

Section: Discussionmentioning

confidence: 99%

Physiological and Molecular Characterization of Atypical Isolates of Malassezia furfur

et al. 2009

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The species constituting the genus Malassezia are considered to be emergent opportunistic yeasts of great importance. Characterized as lipophilic yeasts, they are found in normal human skin flora and sometimes are associated with different dermatological pathologies. We have isolated seven Malassezia species strains that have a different Tween assimilation pattern from the one typically used to differentiate M. furfur, M. sympodialis, and M. slooffiae from other Malassezia species. In order to characterize these isolates of Malassezia spp., we studied their physiological features and conducted morphological and molecular characterization by PCR-restriction fragment length polymorphism and sequencing of the 26S and 5.8S ribosomal DNA-internal transcribed spacer 2 regions in three strains from healthy individuals, four clinical strains, and eight reference strains. The sequence analysis of the ribosomal region was based on the Blastn algorithm and revealed that the sequences of our isolates were homologous to M. furfur sequences. To support these findings, we carried out phylogenetic analyses to establish the relationship of the isolates to M. furfur and other reported species. All of our results confirm that all seven strains are M. furfur; the atypical assimilation of Tween 80 was found to be a new physiological pattern characteristic of some strains isolated in Colombia.The genus Malassezia comprises lipophilic yeasts found in the normal flora of human skin and other mammals. These yeasts were described by Eichstedt in 1848 as being associated with pityriasis versicolor (PV) lesions (13). The taxonomy and nomenclature of the genus Malassezia was controversial for many decades. Indeed, until 1990 only three species were recognized: M. furfur, M. sympodialis, and M. pachydermatis, a non-lipid-dependent species (17,21,38 (4,6,11,17,18,20,21,26,34,38,(40)(41)(42).Malassezia species have been associated with diverse dermatological pathologies, including PV, seborrheic dermatitis dandruff, atopic dermatitis, folliculitis, psoriasis, onicomycosis, and blepharitis. M. furfur and M. pachydermatis have been associated with systemic infections in patients with underlying diseases and those receiving intravenous lipid emulsions (6, 7, 9-11, 16, 29, 33, 34).Although the role of Malassezia species in the development of these diseases is not clear, some authors suggest that M. globosa is the causal agent of PV, while others have found a greater percentage of isolates of M. sympodialis associated with the disease. Differences in diagnosis might be due to sampling methods and differences between the culture media used, leading to controversies in clinical studies of these dermatological pathologies (1, 7, 9, 10). New physiological patterns for identification have been described, and recently the availability of molecular biology and sequencing techniques has allowed the species to be distinguished more clearly (17-21). Despite the difficulty in isolating, maintaining, and identifying these yeasts, different characteristics of ...

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Gene regulation and host adaptation mechanisms in Candida albicans

Cited by 21 publications

References 48 publications

Candida albicans RFX2 Encodes a DNA Binding Protein Involved in DNA Damage Responses, Morphogenesis, and Virulence

Candida albicans RFX2 Encodes a DNA Binding Protein Involved in DNA Damage Responses, Morphogenesis, and Virulence

Phenotypic Switching in Candida lusitaniae on Copper Sulfate Indicator Agar: Association with Amphotericin B Resistance and Filamentation

Physiological and Molecular Characterization of Atypical Isolates of Malassezia furfur

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