Genetic Analysis of Candida albicans Morphological Mutants

Pomés, Rosalina; Gil, Concha; Nombela, César

doi:10.1099/00221287-131-8-2107

Cited by 50 publications

(56 citation statements)

References 30 publications

(20 reference statements)

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“…Most strains of C. albicans and related species are capable of switching spontaneously and reversibly at high frequency among a number of phenotypes distinguishable by colony morphology (10,32,40,43,44). In the case of C albicans WO-1, it has been demonstrated that switching between the white and opaque phases affects not only colony morphology, but also a number of basic physiological and structural characteristics of the budding cell (2-4, 17, 21, 22, 35, 41, 45).…”

Section: Discussionmentioning

confidence: 99%

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Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans.

Morrow¹,

Srikantha²,

Soll³

1992

Mol. Cell. Biol.

144

196

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Cells of Candida albicans WO-1 spontaneously switch between a white and opaque CFU, and this phase transition involves a dramatic change in cellular phenotype. By using a differential hybridization screen, an opaque-specific cDNA, Opla, which represents the transcript of a gene regulated by that it represents the transcript of an acid protease gene of C. albicans, a member of the pepsinogen family. MATERIALS AND METHODSGrowth and development. Cells from C. albicans WO-1 were stored on agar slants in capped tubes. For experimental purposes, cells from a storage slant were clonally plated on agar containing the nutrient composition of Lee's medium (27) supplemented with 70 ,ug of arginine per ml and 0.1 ,M ZnSO4 (7), which we will refer to as modified Lee's medium. Cells from white and opaque colonies were independently diluted into 25 ml of liquid modified Lee's medium, and cultures were rotated at 200 rpm at 25°C as previously described (7,46). The method of pH-regulated dimorphism (11,42)

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Section: Discussionmentioning

confidence: 99%

“…C. albicans and related species are capable of switching between a number of phenotypes usually distinguishable by colony morphology (32,40,41,47). In the case of strain WO-1, switching involves a phase transition between white and opaque colony formation, and this transition includes a dramatic change in cellular phenotype (2-4, 35, 41, 45).…”

mentioning

confidence: 99%

Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans.

Morrow¹,

Srikantha²,

Soll³

1992

Mol. Cell. Biol.

144

196

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“…Such unusual colonies can be isolated from nature, can arise spontaneously in the laboratory (1,2,7,8,13,15,22,29,38,40,46), or can be induced by UV irradiation or chemical agents (14,19,33,38). The genetic basis for their formation was previously unknown (see reference 32).…”

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confidence: 99%

Chromosomal rearrangements associated with morphological mutants provide a means for genetic variation of Candida albicans

1990

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At frequencies as high as 1.4%, the pathogenic yeast Candida albicans spontaneously gave rise to morphological mutants exhibiting more than 20 different types of abnormal colonies; approximately two-thirds of the mutants were stable, while the other one-third were unstable and produced mixtures of different colonial forms at very high rates. Abnormal electrophoretic karyotypes were observed for all of the 14 mutants that were examined, indicating that they were associated with different types of single and multiple gross chromosomal rearrangements. Because C. albicans is asexual and does not go through a meiotic cycle, we suggest that the high frequency of chromosomal rearrangements provides a means for genetic variation in this organism.Since 1935, numerous investigators have reported that the pathogenic yeast Candida albicans produces abnormal colonies, which have been referred to as R type (29), rough variants (1,7,8,46), lethal variants, membranous variants or wrinkled colonies (22), and minute-rough variants (15) as well as by special terms such as star, ring, fuzzy, etc., denoting specific colonial types (38). Such unusual colonies can be isolated from nature, can arise spontaneously in the laboratory (1,2,7,8,13,15,22,29,38,40,46), or can be induced by UV irradiation or chemical agents (14,19,33,38). The genetic basis for their formation was previously unknown (see reference 32).In this paper, we call mutants arising from a normal strain morphological mutants if they have altered colony form, color, size, or texture (28), although this term has also been used to designate morphogenesis mutants (31). We report here the isolation and characterization of spontaneous morphological mutants and demonstrate that such morphological mutants are associated with different types of multiple chromosomal aberrations. Because the morphological mutants arise spontaneously at a high frequency, we suggest that chromosomal aberrations provide a means of genetic variation in this pathogenic amictic microorganism.While this article was in preparation, Suzuki et al. (43) described a morphological mutant with two additional bands in the electrophoretic karyotype. This mutant, in turn, produced revertantlike smooth colonies with differently altered karyotypes at a high frequency of 5 x 10-3. MATERIALS AND METHODS Strains. A collection of spontaneous mutants was isolated from C. albicans 3153A (standard strain) which has also been designated ATCC 32354, 300, and 3153A-SG (13; H. R. Buckley, unpublished result).The haploid strain 867 and diploid strain 7255/4C of Saccharomyces cerevisiae are standard laboratory strains (P. Wakem and F. Sherman, unpublished results) that were used for references of DNA content and for chromosomal markers in pulsed-field electrophoresis.Media. YPD medium contained 1% yeast extract (Difco * Corresponding author.Laboratories), 2% Bacto-Peptone, and 2% glucose, with 2% Bacto-Agar when required for solid medium (37). LBC synthetic medium (21) was initially developed to monitor yeast-hypha transition, an...

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“…Specific subfragments were tested for their ability to compete with the entire domain in the formation of complexes with white-phase protein extract in order to map the proximal domain sequence involved in white-phase-specific complex formation. Our results indicate that white-phase-specific transcription of WH11 is positively regulated by trans-acting factors interacting with two cis-acting activation sequences in the WH11 promoter.As is the case for a number of microbial pathogens (4,11,12,36), Candida albicans switches spontaneously, reversibly, and at high frequencies between a number of general phenotypes, distinguishable by colony morphology (21,24,26). However, switching in C. albicans differs from switching in other microbial pathogens because of its pleiotropic consequences (26).…”

mentioning

confidence: 99%

“…As is the case for a number of microbial pathogens (4,11,12,36), Candida albicans switches spontaneously, reversibly, and at high frequencies between a number of general phenotypes, distinguishable by colony morphology (21,24,26). However, switching in C. albicans differs from switching in other microbial pathogens because of its pleiotropic consequences (26).…”

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confidence: 99%

Functional Analysis of the Promoter of the Phase-Specific WH11 Gene of Candida albicans

Srikantha

Chandrasekhar

Soll

1995

Molecular and Cellular Biology

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Candida albicans WO-1 switches spontaneously, frequently, and reversibly between a hemispherical white and a flat gray (opaque) colony-forming phenotype. This transition affects a number of morphological and physiological parameters and involves the activation and deactivation of phase-specific genes. The WH11 gene is transcribed in the white but not the opaque phase. A chimeric WH11-firefly luciferase gene containing the 5 upstream region of WH11 was demonstrated to be under phase regulation regardless of the site of integration, and a series of promoter deletion constructs was used to delineate two white-phase-specific transcription activation domains. Gel retardation experiments with the individual distal or proximal domain and white-phase or opaque-phase protein extract demonstrated the formation of one distal white-phasespecific complex and two proximal white-phase-specific complexes. Specific subfragments were tested for their ability to compete with the entire domain in the formation of complexes with white-phase protein extract in order to map the proximal domain sequence involved in white-phase-specific complex formation. Our results indicate that white-phase-specific transcription of WH11 is positively regulated by trans-acting factors interacting with two cis-acting activation sequences in the WH11 promoter.As is the case for a number of microbial pathogens (4,11,12,36), Candida albicans switches spontaneously, reversibly, and at high frequencies between a number of general phenotypes, distinguishable by colony morphology (21,24,26). However, switching in C. albicans differs from switching in other microbial pathogens because of its pleiotropic consequences (26). In the white-opaque transition in strain WO-1 (25), a switch between a hemispherical white and a flat grey (opaque) colony morphology affects cell size, cell mass, wall morphology, budding pattern, sugar assimilation pattern, adhesion, drug susceptibility, sensitivity to oxidants, and patterns of tissue invasion in systemic mouse models (reviewed in references 26 and 28). The pleiotropy of this transition suggested that it involved the coordinate regulation of phase-specific genes, and differences in the in vitro translation products of white-phase and opaque-phase RNAs supported this hypothesis (27). The hypothesis was verified by the isolation and characterization of white-phase-specific and opaque-phase-specific genes. In the opaque phase, cells differentially express the opaque-phasespecific genes PEP1 (19), which encodes a secreted aspartyl proteinase (13) and is also referred to as SAP1 (40); SAP3, which encodes a second secreted aspartyl proteinase (40); and Op4 (18), which encodes a unique protein which is selectively expressed not only in the opaque phase of strain WO-1 but also in the variant phenotypes of strain 3153A (17). In the white phase, cells differentially express the white-phase-specific gene WH11 (33), which encodes a protein homologous to the glucose-lipid-regulated GLP1 protein of Saccharomyces cerevisiae (34). Since th...

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Genetic Analysis of Candida albicans Morphological Mutants

Cited by 50 publications

References 30 publications

Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans.

Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans.

Chromosomal rearrangements associated with morphological mutants provide a means for genetic variation of Candida albicans

Functional Analysis of the Promoter of the Phase-Specific WH11 Gene of Candida albicans

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