Cytoplasmic localization of the white phasespecific WH11 gene product of Candida albicans

Schröppel, Klaus; Srikantha, Thyagarajan; Wessels, Deborah; DeCock, Melanie; Lockhart, Shawn R.; Soll, David R.

doi:10.1099/13500872-142-8-2245

Cited by 13 publications

(24 citation statements)

References 32 publications

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“…There are reasons to believe that RLUC levels do indeed reflect transcriptional states. While stationary-phase cells and budding cells contain the Wh11 protein, as demonstrated by indirect immunofluorescent staining with anti-Wh11 antiserum, contain WH11 mRNA, and express RLUC when it is under the regulation of the Wh11 promoter, cells which have just extended a germ tube (i.e., an incipient hypha) are devoid of Wh11 antigen, do not contain WH11 mRNA, and contain dramatically reduced levels of RLUC activity when RLUC is under the regulation of the WH11 promoter (14,25). In addition, the relative levels of reporter transcript in the various deletion derivatives in the original promoter analysis (22) were highly similar to the relative levels of RLUC activity measured in the comparative deletion derivatives in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…It was previously demonstrated that cells which formed buds at pH 4.5 contained both the WH11 transcript (25) and WH11 protein (14), but cells which formed hyphae at pH 6.7 contained neither transcript (25) nor protein (14). To characterize the kinetics of the loss of RLUC activity in a cell population induced to form hyphae, cells harboring the transcriptional fusion derivative pCRW5⌬6 were analyzed under the regime of pH-regulated dimorphism.…”

Section: Wh11mentioning

confidence: 99%

“…WH11 is expressed in the budding white phase but is inactive after cells have differentiated to a hypha or have switched to the opaque phase. Wh11 is homologous to the glucose lipid-regulated protein Glp1p of Saccharomyces cerevisiae (26), which has also been identified as heat shock protein HSP12 (9), and is distributed throughout the cytoplasm of white budding C. albicans cells (14). The Wh11 protein is undetectable in opaque-phase cells and in white budding cells which have just formed hyphae (14).…”

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confidence: 99%

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The WH11 gene of Candida albicans is regulated in two distinct developmental programs through the same transcription activation sequences

1997

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Candida albicans strain WO-1 undergoes two developmental programs, the bud-hypha transition and highfrequency phenotypic switching in the form of the white-opaque transition. The WH11 gene is expressed in the white budding phase but is inactive in the white hyphal phase and in the opaque budding phase. WH11 expression, therefore, is regulated in the two developmental programs. Through fusions between deletion derivatives of the WH11 promoter and the newly developed Renilla reniformis luciferase, the WH11 promoter has been characterized in the two developmental programs. Three transcription activation sequences, two strong and one weak, are necessary for the full expression of WH11 in the white budding phase, but no negative regulatory sequences were revealed as playing a role in either the white hyphal phase or the opaque budding phase. These results suggest that regulation is solely through activation in the white budding phase and the same mechanism, therefore, is involved in regulating the differential expression of WH11 in the alternative white and opaque phases of switching and the budding and hyphal phases of dimorphism.Candida albicans and a number of related species possess two well-defined developmental programs, the bud-hypha transition (16) and high-frequency phenotypic switching (17). In the bud-hypha transition, cells differentiate from a round, budding growth form to an elongate hyphal growth form, the latter composed of sequential cellular compartments. The hyphal growth form represents a morphological modification which apparently facilitates foraging and tissue penetration. In the program of high-frequency phenotypic switching, cells switch spontaneously and reversibly between a number of general phenotypes distinguishable by alterations in colony morphology. Phenotypic switching can also have extreme pleiotropic consequences on cellular phenotype (2,15,17,19,20).Although the bud-hypha transition and high-frequency phenotypic switching represent two distinguishable developmental programs, there are several indications in the most thoroughly analyzed switching system, the white-opaque transition in strain , that the regulatory circuitry in the two programs partially overlaps. First, opaque-phase cells, like hyphae, are elongate, and each contains a large vacuole similar to the one observed in each hyphal compartment (2). Second, opaque-phase cells express one or more hypha-specific surface antigens, although they also express opaque-phase-specific surface antigens (1). Third, an analysis of the transition from white to opaque at the single-cell level suggested a pseudohyphal intermediate (4,20). Finally, the white-phase-specific gene WH11 is not only under the control of the white-opaque transition but also under the control of the bud-hypha transition (25). WH11 is expressed in the budding white phase but is inactive after cells have differentiated to a hypha or have switched to the opaque phase. Wh11 is homologous to the glucose lipid-regulated protein Glp1p of Saccharomyces cerevisiae (26), wh...

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Section: Discussionmentioning

confidence: 99%

Section: Wh11mentioning

confidence: 99%

mentioning

confidence: 99%

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The WH11 gene of Candida albicans is regulated in two distinct developmental programs through the same transcription activation sequences

1997

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“…Over the past several years we (19 -24) and others (25)(26)(27)(28)(29)(30)(31)(32) have been investigating specific Ab induction as an immunotherapeutic preventive measure against the development of candidiasis. We have developed a vaccine for active immunization and have discovered protective mAbs; both approaches have shown efficacious promise against experimental, hematogenously disseminated candidiasis and against vaginal infection due to C. albicans.…”

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confidence: 99%

Complement Is Essential for Protection by an IgM and an IgG3 Monoclonal Antibody Against Experimental, Hematogenously Disseminated Candidiasis

Kozel

Zhang

et al. 2001

The Journal of Immunology

134

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The incidence of life-threatening, hematogenously disseminated candidiasis, which is predominantly caused by Candida albicans, parallels the use of modern medical procedures that adversely affect the immune system. Limited antifungal drug choices and emergence of drug-resistant C. albicans strains indicate the need for novel prevention and therapeutic strategies. We are developing vaccines and Abs that enhance resistance against experimental candidiasis. However, the prevalence of serum anti-Candida Abs in candidiasis patients has led to the misconception that Abs are not protective. To explain the apparent discrepancy between such clinical observations and our work, we compared functional activities of C. albicans-specific protective and nonprotective mAbs. Both kinds of Abs are agglutinins that fix complement and are specific for cell surface mannan, but the protective Abs recognize β-mannan, and the nonprotective Ab is specific for α-mannan. By several indirect and direct measures, the protective mAbs more efficiently bind complement factor C3 to the yeast cell than do nonprotective Ab. We hypothesize that the C3 deposition causes preferential association of blood-borne fungi with host phagocytic cells that are capable of killing the fungus. We conclude from these results that the protective potential of Abs is dependent on epitope specificity, serum titer, and ability to rapidly and efficiently fix complement to the fungal surface. The mechanism of protection appears to be associated with enhanced phagocytosis and killing of the fungus.

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“…The WH11 gene encodes a protein with homology to the heat shock protein Hsp12 and is localized in the cytoplasm of white cells (33). The SAP genes encode secreted aspartic proteinases that have been shown to contribute to the virulence of WO-1 and other C. albicans strains (14,16).…”

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Analysis of Phase-Specific Gene Expression at the Single-Cell Level in the White-Opaque Switching System of Candida albicans

2001

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The opportunistic fungal pathogen Candida albicans can switch spontaneously and reversibly between different cell forms, a capacity that may enhance adaptation to different host niches and evasion of host defense mechanisms. Phenotypic switching has been studied intensively for the white-opaque switching system of strain WO-1. To facilitate the molecular analysis of phenotypic switching, we have constructed homozygous ura3 mutants from strain WO-1 by targeted gene deletion. The two URA3 alleles were sequentially inactivated using the MPA R -flipping strategy, which is based on the selection of integrative transformants carrying a mycophenolic acid (MPA) resistance marker that is subsequently deleted again by site-specific, FLP-mediated recombination. To investigate a possible cell type-independent switching in the expression of individual phasespecific genes, two different reporter genes that allowed the analysis of gene expression at the single-cell level were integrated into the genome, using URA3 as a selection marker. Fluorescence microscopic analysis of cells in which a GFP reporter gene was placed under the control of phase-specific promoters demonstrated that the opaque-phase-specific SAP1 gene was detectably expressed only in opaque cells and that the white-phasespecific WH11 gene was detectably expressed only in white cells. When MPA R was used as a reporter gene, it conferred an MPA-resistant phenotype on opaque but not white cells in strains expressing it from the SAP1 promoter, which was monitored at the level of single cells by a significantly enlarged size of the corresponding colonies on MPA-containing indicator plates. Similarly, white but not opaque cells became MPA resistant when MPA R was placed under the control of the WH11 promoter. The analysis of these reporter strains showed that cell type-independent phase variation in the expression of the SAP1 and WH11 genes did not occur at a detectable frequency. The expression of these phase-specific genes of C. albicans in vitro, therefore, is tightly linked to the cell type.

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Cytoplasmic localization of the white phasespecific WH11 gene product of Candida albicans

Cited by 13 publications

References 32 publications

The WH11 gene of Candida albicans is regulated in two distinct developmental programs through the same transcription activation sequences

The WH11 gene of Candida albicans is regulated in two distinct developmental programs through the same transcription activation sequences

Complement Is Essential for Protection by an IgM and an IgG3 Monoclonal Antibody Against Experimental, Hematogenously Disseminated Candidiasis

Analysis of Phase-Specific Gene Expression at the Single-Cell Level in the White-Opaque Switching System of Candida albicans

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