scholarly journals Recent advances in understanding Candida albicans hyphal growth

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 700 ◽  
Author(s):  
Robert A. Arkowitz ◽  
Martine Bassilana

Morphological changes are critical for the virulence of a range of plant and human fungal pathogens. Candida albicans is a major human fungal pathogen whose ability to switch between different morphological states is associated with its adaptability and pathogenicity. In particular, C. albicans can switch from an oval yeast form to a filamentous hyphal form, which is characteristic of filamentous fungi. What mechanisms underlie hyphal growth and how are they affected by environmental stimuli from the host or resident microbiota? These questions are the focus of intensive research, as understanding C. albicans hyphal growth has broad implications for cell biological and medical research.

Antibiotics ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 10 ◽  
Author(s):  
Olena P. Ishchuk ◽  
Olov Sterner ◽  
Ulf Ellervik ◽  
Sophie Manner

The opportunistic human fungal pathogen Candida albicans relies on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-l-fucopyranoside and benzyl β-d-xylopyranoside, inhibit the hyphae formation and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-l-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-d-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.


2019 ◽  
Author(s):  
Olena P. Ishchuk ◽  
Olov Sterner ◽  
Ulf Ellervik ◽  
Sophie Manner

Abstract The opportunistic human fungal pathogen Candida albicans rely on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-L-fucopyranoside and benzyl β-D-xylopyranoside, inhibit the morphological switching and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-L-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-D-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.


2019 ◽  
Author(s):  
Ognenka Avramovska ◽  
Meleah A. Hickman

AbstractOrganismal ploidy state and environmental stress impact the mutational spectrum and the mutational rate. The human fungal pathogen Candida albicans, serves as a clinically relevant model for studying the interaction between eukaryotic ploidy and stress-induced mutagenesis. In this study, we compared the rates and types of genome perturbations in diploid and tetraploid C. albicans following exposure to two classes of antifungal drugs, azoles and echinocandins. We measured mutations at three different scales: point mutation, loss-of-heterozygosity (LOH), and genome size changes in cells treated with fluconazole and caspofungin. We find that caspofungin induced higher rates of mutation than fluconazole, likely an indirect result from the stress associated with cell wall perturbations rather than an inherent genotoxicity. Furthermore, we found disproportionately elevated rates of LOH and genome size changes in response to both antifungals in tetraploid C. albicans compared to diploid C. albicans, suggesting that the magnitude of stress-induced mutagenesis results from an interaction between ploidy state and the environment. These results have both clinical and evolutionary implications for how fungal pathogens generate mutations in response to antifungal drug stress, and may facilitate the emergence of antifungal resistance.


2019 ◽  
Author(s):  
Olena P. Ishchuk ◽  
Olov Sterner ◽  
Ulf Ellervik ◽  
Sophie Manner

Abstract The opportunistic human fungal pathogen Candida albicans rely on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-L-fucopyranoside and benzyl β-D-xylopyranoside, inhibit the morphological switching and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-L-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-D-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.


2018 ◽  
Author(s):  
Lucian Duvenage ◽  
Louise A. Walker ◽  
Aleksandra Bojarczuk ◽  
Simon A. Johnston ◽  
Donna M. McCallum ◽  
...  

AbstractThe human fungal pathogenCandida albicanspossesses two genes expressing a cyanide-insensitive Alternative Oxidase (Aox) enzymes in addition to classical and parallel electron transfer chains (ETC). In this study, we examine the role of Aox inC.albicansunder conditions of respiratory stress, which may be inflicted during its interaction with the human host or co-colonising bacteria. We find that the level of Aox expression is sufficient to modulate resistance to classical ETC inhibition under respiratory stress and are linked to gene expression changes that can promote both survival and pathogenicity. For example we demonstrate that Aox function is important for the regulation of filamentation inC.albicansand observe that cells lacking Aox function lose virulence in a zebrafish infection model. Our investigations also identify that pyocyanin, a phenazine produced by the co-colonising bacteriumPseudomonas aeruginosa, inhibits Aox-based respiration inC.albicans. These results suggest that Aox plays important roles within respiratory stress response pathways whichC.albicansmay utilise both as a commensal organism and as a pathogen.


2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Guolei Zhao ◽  
Laura Rusche

Candida albicans is a major human fungal pathogen that encounters varied host environments during infection. In response to environmental cues, C. albicans switches between ovoid yeast and elongated hyphal growth forms, and this morphological plasticity contributes to virulence. Environmental changes that alter the cell’s metabolic state could be sensed by sirtuins, which are NAD+-dependent deacetylases. Here we studied the roles of three sirtuin deacetylases, Sir2, Hst1, and Hst2, in hyphal growth of C. albicans. We made single, double, and triple sirtuin knockout strains and tested their ability to switch from yeast to hyphae. We found that true hyphae formation was significantly reduced by the deletion of SIR2 but not HST1 or HST2. Moreover, the expression of hyphal-specific genes HWP1, ALS3, and ECE1 decreased in the sir2Δ/Δ mutant compared to wild-type. This regulation of hyphae formation was dependent on the deacetylase activity of Sir2, as a point mutant lacking deacetylase activity had a similar defect in hyphae formation as the sir2Δ/Δ mutant. Finally, we found that Sir2 and Hst1 were localized to the nucleus, with Sir2 specifically focused in the nucleolus. This nuclear localization suggests a role for Sir2 and Hst1 in regulating gene expression. In contrast, Hst2 was localized to the cytoplasm. In conclusion, our results suggest that Sir2 plays a critical and non-redundant role in hyphal growth of C. albicans.


2005 ◽  
Vol 16 (6) ◽  
pp. 2772-2785 ◽  
Author(s):  
Avigail Atir-Lande ◽  
Tsvia Gildor ◽  
Daniel Kornitzer

The ability of Candida albicans, a major fungal pathogen, to switch between a yeast form, and a hyphal (mold) form is recognized as being important for the ability of the organism to invade the host and cause disease. We found that a C. albicans mutant deleted for CaCDC4, a homologue of the Saccharomyces cerevisiae F-box protein component of the SCFCDC4ubiquitin ligase, is viable and displays constitutive filamentous, mostly hyphal, growth. The phenotype of the Cacdc4–/– mutant suggests that ubiquitin-mediated protein degradation is involved in the regulation of the dimorphic switch of C. albicans and that one or more regulators of the yeast-to-mold switch are among the substrates of SCFCaCDC4. Epistasis analysis indicates that the Cacdc4–/– phenotype is largely independent of the filamentation-inducing transcription factors Efg1 and Cph1. We identify C. albicans Far1 and Sol1, homologues of the S. cerevisiae SCFCDC4substrates Far1 and Sic1, and show that Sol1 is a substrate of C. albicans Cdc4. Neither protein is essential for the hyphal phenotype of the Cacdc4–/– mutant. However, ectopic expression and deletion of SOL1 indicate a role for this gene in C. albicans morphogenesis.


2017 ◽  
Vol 8 ◽  
Author(s):  
Julien Chaillot ◽  
Faiza Tebbji ◽  
Carlos García ◽  
Hugo Wurtele ◽  
René Pelletier ◽  
...  

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