The gray phenotype and tristable phenotypic transitions in the human fungal pathogen Candida tropicalis

Li, Tao; Zhang, Qiuyu; Guan, Guijian; Nobile, Clarissa J.; Zheng, Qiushi; Ding, Xuefen; Huang, Guanghua

doi:10.1016/j.fgb.2016.05.006

Cited by 13 publications

(14 citation statements)

References 20 publications

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“…Functional descriptions and roles of C. albicans ortholog were according to the CGD database (http://www.candidagenome.org/). Cell type enrichment in C. tropicalis data was adapted from references (Porman et al ., ; Anderson et al ., ; Zhang et al ., ). The WT and WT + vector control strains belong to SW‐3 (20–50%).…”

Section: Resultsmentioning

confidence: 97%

“…In C. tropicalis , GlcNAc promotes the opaque phenotype but has a repressing effect on filamentation (Xie et al ., ). Recently, we and the Bennett laboratory have reported a tristable switching system in C. tropicalis (Anderson et al ., ; Zhang et al ., ). We found a novel phenotype, the gray phenotype, whereas the Bennett laboratory reported a similar ‘hybrid’ cell type in C. tropicalis .…”

Section: Introductionmentioning

confidence: 97%

“…Both gray and hybrid cells of C. tropicalis are elongated but smaller than opaque cells and regulated by the transcription factors Wor1 and Efg1. Together with the white and opaque cell types, the gray or hybrid cell type forms a white‐gray (hybrid)‐opaque tristable switching system in C. tropicalis (Anderson et al ., ; Zhang et al ., ).…”

Section: Introductionmentioning

confidence: 97%

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Environmental and genetic regulation of white‐opaque switching in Candida tropicalis

Zheng

Zhang

Jian

et al. 2017

Molecular Microbiology

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Phenotypic switching is a strategy by which microbial organisms adapt to environmental changes. The human fungal pathogens, Candida albicans and Candida tropicalis, are closely related species and capable of undergoing morphological transitions. C. albicans primarily exists in human or warm-blooded animals as a commensal, whereas C. tropicalis not only exists as a commensal but also is widely distributed in the environment. In this study, we describe the environmental and genetic regulatory mechanisms of white-opaque switching in C. tropicalis, which is associated with virulence and sexual mating. A comparative study with C. albicans demonstrated that C. tropicalis responds to environmental stimuli, such as elevated CO levels and pH changes, in opposite manners. An acidic pH and elevated CO levels promote the opaque phenotype in C. albicans but have an opposite effect in C. tropicalis, whereas alkaline pH conditions facilitate white-to-opaque switching and sexual mating in C. tropicalis. The conserved Rim101-mediated pH sensing and Ras1-cAMP/PKA signaling pathways are involved in this regulation. By screening an overexpression library of transcription factors, we identified 26 white-opaque regulators, including WOR1, AHR1, EFG1, CUP9, BCR1 and SFL2. Transcriptional analysis indicated that the pH sensing and Ras1-cAMP/PKA signaling pathways and transcriptional regulators coordinately regulate white-to-opaque switching.

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

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Environmental and genetic regulation of white‐opaque switching in Candida tropicalis

Zheng

Zhang

Jian

et al. 2017

Molecular Microbiology

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“…Total RNA was extracted using GeneJET RNA Purification kits according to the manufacturer's instructions. Quantitative RT‐PCR assays were performed as previous described (Xie et al ., ; Zhang et al ., ). The signal from each experimental sample was normalized to expression of the ACT1 gene.…”

Section: Methodsmentioning

confidence: 99%

“…White cells can be induced to form filaments in response to serum, neutral pH and Lee's medium at 378C, whereas opaque cells cannot undergo filamentation under these standard filamentinducing laboratory conditions (Anderson et al, 1989;Guan et al, 2013;Si et al, 2013). In addition to white and opaque cell types, we recently discovered a novel heritable cell type, the grey phenotype, in C. albicans, Candida dubliniensis and Candida tropicalis (Tao et al, 2014;Yue et al, 2016;Zhang et al, 2016). Grey cells exhibit a set of distinct biological features from white and opaque cells, and the ability to switch between these three distinct cell states is likely important for adaptation of Candida species to the host environment.…”

Section: Introductionmentioning

confidence: 99%

Lactic acid bacteria differentially regulate filamentation in two heritable cell types of the human fungal pathogen Candida albicans

Liang

Guan

Dai

et al. 2016

Molecular Microbiology

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Microorganisms rarely exist as single species in natural environments. The opportunistic fungal pathogen Candida albicans and lactic acid bacteria (LAB) are common members of the microbiota of several human niches such as the mouth, gut, and vagina. LAB are known to suppress filamentation, a key virulence feature of C. albicans, through the production of lactic acid and other metabolites. Here we report that C. albicans cells switch between two heritable cell types, white and opaque, to undergo filamentation to adapt to diversified environments. We show that acidic pH conditions caused by LAB and low temperatures support opaque cell filamentation, while neutral pH conditions and high temperatures promote white cell filamentation. The cAMP signaling pathway and the Rfg1 transcription factor play major roles in regulating the responses to these conditions. This cell type-specific response of C. albicans to different environmental conditions reflects its elaborate regulatory control of phenotypic plasticity.

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Deciphering Colonies of Phenotypic Switching-Derived Morphotypes of the Pathogenic Yeast Candida tropicalis

et al. 2022

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Background Phenotypic switching generates fungal colonies with altered morphology and allows pathogens to adapt to changing environments.Objective This study investigated the structure of switched colonies in Candida tropicalis.Methods The switched variant strains (crepe and rough) were analyzed for colony morphology at the ultrastructural level-SEM. The distribution and composition of the extracellular matrix (ECM) were evaluated. The percentage of hyphae was determined by direct counting using light microscopy. The gene expression for these responses was measured by RT-qPCR. ResultsThe macromorphology of the switched variants exhibited high complexity, showing depressions, irregular edges, and a greater amount of ECM than the original strain. In addition, rough variant colonies showed higher amounts of total carbohydrates and proteins in ECM (p<0.05). We also observed a positive correlation between BCR1 (Bio lm cell regulator) gene expression and carbohydrate content in the rough variant (Pearson Correlation r²=0.9885, p=0.0483). Structured colonies exhibited a higher percentage of hyphae throughout their development (p<0.05). EFG1 (Enhanced lamentous growth protein 1) and WOR1 (White-opaque regulator 1) gene expression were positively correlated to the hyphae formation pro le of the structured and unstructured (original strain) patterns (r²>0.7673, p<0.05).Conclusion Structural variations in switched morphotypes colonies of C. tropicalis are associated with increased hyphae growth and distinction in composition and distribution of ECM. Switched phenotypes exhibit features that may contribute to the success of infection associated with C. tropicalis.

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The gray phenotype and tristable phenotypic transitions in the human fungal pathogen Candida tropicalis

Cited by 13 publications

References 20 publications

Environmental and genetic regulation of white‐opaque switching in Candida tropicalis

Environmental and genetic regulation of white‐opaque switching in Candida tropicalis

Lactic acid bacteria differentially regulate filamentation in two heritable cell types of the human fungal pathogen Candida albicans

Deciphering Colonies of Phenotypic Switching-Derived Morphotypes of the Pathogenic Yeast Candida tropicalis

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