scholarly journals CRISPR-Cas9 mutagenesis and single gene reintegration suggests functional diversity within the Candida albicans TLO gene family

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Jessica Fletcher ◽  
Gary Moran ◽  
Derek Sullivan
Keyword(s):  
Growth Rate ◽  
Candida Albicans ◽  
Gene Family ◽  
Biofilm Formation ◽  
Single Gene ◽  
Hyphal Growth ◽  
Detectable Effect ◽  
Null Mutant ◽  
Phenotypic Analysis ◽  
Functional Differences

Candida albicans has between 10-15 Telomere-associated ORF family(TLO)genes, whereas its closest relative, Candida dubliniensis, has two. The Tlo proteins are components of the Mediator complex which plays an important role in transcriptional regulation. CRISPR-Cas9 mutagenesis was used to generate a TLOnull mutant of C. albicans. Phenotypic analysis of the mutant showed significantly reduced fitness, with major defects in growth rate, morphogenesis, stress resistance and virulence in a Galleria mellonellamodel. Clade representative TLOα1, TLOβ2 and TLOγ11constructs were reintroduced into the null mutant background to determine if members of the TLO gene family exhibit functional differences. The genes were reintroduced under the control of the TET1 and ENO1promoters. TLOα1and TLOβ2expression restored stress tolerance and growth rate, in some cases to the level of the WT. TLOβ2expression also showed a dramatic effect on morphology resulting in constitutive true hyphal growth. Moderate expression of TLOγ11 had no detectable effect on many of the phenotypes tested, however overexpression increased biofilm formation in Spider medium, and also conferred increased resistance to cell wall stressors. These data suggest that individual TLO genes have distinct functions and that the diversity within the TLO family may contribute to the relative success of C. albicans as a coloniser and pathogen of humans.

Zerumbone inhibits Candida albicans biofilm formation and hyphal growth

2019 ◽  
Vol 65 (10) ◽  
pp. 713-721 ◽  
Author(s):  
Da-Seul Shin ◽  
Yong-Bin Eom
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Antifungal Agents ◽  
Hyphal Growth ◽  
Antibiofilm Activity ◽  
Potential Candidate ◽  
Zingiber Zerumbet ◽  
Dna Contents ◽  
Important Virulence Factor ◽  
Morphologic Changes

Candida albicans biofilm formation is considered an important matter because it can lead to strong resistance to conventional antifungal agents. Hyphae formed by C. albicans can also act as an important virulence factor related to its biofilm. The objective of this study was to determine the effect of zerumbone, a monocyclic sesquiterpene extracted from Zingiber zerumbet (L.) Smith, against C. albicans biofilm formation. Our results suggest that zerumbone possesses antifungal and antibiofilm activity that inhibits biofilm formation and eradicates preformed biofilm. Notably, zerumbone considerably reduced carbohydrate and DNA contents of biofilm matrix. In addition, zerumbone showed antivirulence effects by decreasing the growth of hyphae and inhibiting morphologic changes of C. albicans. Furthermore, zerumbone significantly downregulated expression levels of biofilm-related and hyphae-specific genes, including HWP1 and ALS3. Since zerumbone suppresses biofilm formation and hyphae growth, these results indicate that zerumbone could be used as a potential candidate to treat and prevent C. albicans biofilm-related infections.

Inhibitory effects of the essential oils α-longipinene and linalool on biofilm formation and hyphal growth of Candida albicans

Biofouling ◽  
2017 ◽  
Vol 33 (2) ◽  
pp. 143-155 ◽  
Author(s):  
Ranjith Kumar Manoharan ◽  
Jin-Hyung Lee ◽  
Yong-Guy Kim ◽  
Soon-Il Kim ◽  
Jintae Lee
Keyword(s):  
Candida Albicans ◽  
Essential Oils ◽  
Biofilm Formation ◽  
Hyphal Growth ◽  
Inhibitory Effects

A role of Candida albicans CDC4 in the negative regulation of biofilm formation

2015 ◽  
Vol 61 (4) ◽  
pp. 247-255 ◽  
Author(s):  
Tzu-Ling Tseng ◽  
Wei-Chung Lai ◽  
Tai-Lin Lee ◽  
Wan Hua Hsu ◽  
Yu Wen Sun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Biofilm Formation ◽  
Negative Regulation ◽  
Null Mutant ◽  
Auxotrophic Strain ◽  
Reduction Assay ◽  
Mutant Strains

The CDC4 gene is nonessential in Candida albicans and plays a role in suppressing filamentous growth, in contrast to its homologues, which are involved in the G1–S transition of the cell cycle. While characterizing the function of C. albicans CDC4 (CaCDC4), we found that the loss of CaCDC4 resulted in a reduction in cell flocculation, indicating a possible role for CaCDC4 in biofilm formation. To elucidate the role of CaCDC4 in biofilm formation, Cacdc4 null mutant strains were constructed by using the mini-Ura-blaster method. To create a CaCDC4 rescued strain, the plasmid p6HF-ACT1p-CaCDC4 capable of constitutively expressing CaCDC4 was introduced into the Cacdc4 homozygous null mutant. To determine the biofilm formation ability, an in vitro XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium-5-carboxanilide) reduction assay was used. Compared with the parental auxotrophic strain BWP17, the Cacdc4 homozygous null mutant was able to enhance biofilm formation significantly. This enhancement of biofilm formation in the Cacdc4 homozygous null mutant could be reversed by constitutively expressing CaCDC4. We conclude that CaCDC4 has a role in suppressing biofilm formation in C. albicans.

scholarly journals The vesicle transport protein Vac1p is required for virulence of Candida albicans

Microbiology ◽  
2006 ◽  
Vol 152 (10) ◽  
pp. 3111-3121 ◽  
Author(s):  
Kathrin Franke ◽  
Monika Nguyen ◽  
Albert Härtl ◽  
Hans-Martin Dahse ◽  
Georgia Vogl ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mutant Strain ◽  
Protein Transport ◽  
Systemic Infection ◽  
Hyphal Growth ◽  
Transport Protein ◽  
Vesicle Transport ◽  
Antifungal Drugs ◽  
Null Mutant ◽  
Pathogenic Yeast

The putative vesicle transport protein Vac1p of the human pathogenic yeast Candida albicans plays an important role in virulence. To determine the cellular functions of Vac1p, a null mutant was generated by sequential disruption of both alleles. The vac1 null mutant strain showed defective endosomal vesicle transport, demonstrating a role of Vac1p in protein transport to the vacuole. Vac1p also contributes to resistance to metal ions, as the null mutant strain was hypersensitive to Cu2+, Zn2+ and Ni2+. In addition, the loss of Vac1p affected several virulence factors of C. albicans. In particular, the vac1 null mutant strain showed defective hyphal growth, even when hyphal formation was induced via different pathways. Furthermore, Vac1p affects chlamydospore formation, adherence to human vaginal epithelial cells, and the secretion of aspartyl proteinases (Saps). Avirulence in a mouse model of systemic infection of the vac1 null mutant strongly suggests that Vac1p of C. albicans is essential for pathogenicity. In summary, the Vac1p protein is required for several cellular pathways, in particular those that control virulence and pathogenicity. Consequently, Vac1p is a novel and interesting target for antifungal drugs.

Penicillenols from a deep-sea fungus Aspergillus restrictus inhibit Candida albicans biofilm formation and hyphal growth

2017 ◽  
Vol 70 (6) ◽  
pp. 763-770 ◽  
Author(s):  
Jie Wang ◽  
Qi-Feng Yao ◽  
Muhammad Amin ◽  
Xu-Hua Nong ◽  
Xiao-Yong Zhang ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Deep Sea ◽  
Biofilm Formation ◽  
Hyphal Growth

scholarly journals E1210, a New Broad-Spectrum Antifungal, Suppresses Candida albicans Hyphal Growth through Inhibition of Glycosylphosphatidylinositol Biosynthesis

2011 ◽  
Vol 56 (2) ◽  
pp. 960-971 ◽  
Author(s):  
Nao-aki Watanabe ◽  
Mamiko Miyazaki ◽  
Takaaki Horii ◽  
Koji Sagane ◽  
Kappei Tsukahara ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Inhibitory Activity ◽  
Biofilm Formation ◽  
Protein A ◽  
Hyphal Growth ◽  
Tube Formation ◽  
Protein Maturation ◽  
Content Type ◽  
Protein Levels

ABSTRACTContinued research toward the development of new antifungals that act via inhibition of glycosylphosphatidylinositol (GPI) biosynthesis led to the design of E1210. In this study, we assessed the selectivity of the inhibitory activity of E1210 againstCandida albicansGWT1(Orf19.6884) protein,Aspergillus fumigatusGWT1(AFUA_1G14870) protein, and humanPIG-Wprotein, which can catalyze the inositol acylation of GPI early in the GPI biosynthesis pathway, and then we assessed the effects of E1210 on keyC. albicansvirulence factors. E1210 inhibited the inositol acylation activity ofC. albicansGwt1p andA. fumigatusGwt1p with 50% inhibitory concentrations (IC50s) of 0.3 to 0.6 μM but had no inhibitory activity against human Pig-Wp even at concentrations as high as 100 μM. To confirm the inhibition of fungal GPI biosynthesis, expression ofALS1protein, a GPI-anchored protein, on the surfaces ofC. albicanscells treated with E1210 was studied and shown to be significantly lower than that on untreated cells. However, theALS1protein levels in the crude extract and theRHO1protein levels on the cell surface were found to be almost the same. Furthermore, E1210 inhibited germ tube formation, adherence to polystyrene surfaces, and biofilm formation ofC. albicansat concentrations above its MIC. These results suggested that E1210 selectively inhibited inositol acylation of fungus-specific GPI which would be catalyzed by Gwt1p, leading to the inhibition of GPI-anchored protein maturation, and also that E1210 suppressed the expression of some important virulence factors ofC. albicans, through its GPI biosynthesis inhibition.

scholarly journals Effect of Propolis on the Adhesion Index, Morphology and Viability of Candida albicans Cells on Biofilm Formation

2021 ◽  
Vol 7 (1) ◽  
pp. 1
Author(s):  
Dinda Oktia Maghfiroh ◽  
A.A. Santi Dewi ◽  
Anggie Diniayuningrum ◽  
Bambang Rahardjo ◽  
Nurdiana Nurdiana ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Light Microscopy ◽  
Cell Viability ◽  
Biofilm Formation ◽  
Ethanol Extract ◽  
Hyphal Growth ◽  
Colony Growth ◽  
Vulvovaginal Candidiasis ◽  
The One ◽  
Adhesion Index

About 70-75% of reproductive women have experienced vulvovaginal candidiasis at least once and 40-45% will have recurrences. Candida albicans is the most etiology of vulvovaginal candidiasis and is able to form biofilm that can lead to antifungal resistances and recurrences. One of the natural products that have an antibiofilm effect is propolis. This study expected that propolis from Lawang can be the one of antibiofilm agent candidates to antifungi resistant cases. This study aimed to know the antibiofilm effect of propolis ethanol extract to cell adhesion index, morphology, and viability of Candida albicans cell on biofilm formation. The adhesion index was counted on 100 epithelial cells under light microscopy (1000x). Morphology was seen using light microscopy (400x). Cell viability was examined by CFU assay. At 12.5% concentration of propolis ethanol extract, adhesion index decreased (p=0,000) and hyphal growth was inhibited. Colony growth decreased at 2.5% concentration and was not seen at 10% concentration of propolis ethanol extract (p=0,000). This results indicated that propolis ethanol extract can decrease adhesion index, failed the Candida albicans morphology transition from yeast to hyphal, and decreased Candida albicans cell viability on biofilm formation. Propolis ethanol extract is likely to be one of alternatives to recurrent vulvovaginal candidiasis treatment, especially caused by Candida albicans biofilm formation.

scholarly journals Correction to Inhibition of Biofilm Formation by Candida albicans and Polymicrobial Microorganisms by Nepodin via Hyphal-Growth Suppression

2020 ◽  
Vol 6 (5) ◽  
pp. 1283-1283
Author(s):  
Jin-Hyung Lee ◽  
Yong-Guy Kim ◽  
Sagar Kiran Khadke ◽  
Aki Yamano ◽  
Akio Watanabe ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Hyphal Growth ◽  
Growth Suppression
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