Glabridin triggers over-expression of apoptosis inducing factor (AIF) gene in Candida albicans

Background and Purpose: Candida albicans is a prevalent human fungal pathogen that can cause a wide spectrum of diseases, from superficial mucosal infections to systemic disorders, in patients with impaired immunity. Glabridin is a pyranoisoflavan originally extracted from root extract of Glycyrrhiza glabra. Glabridin can also mediate apoptosis in yeast cells by changing the mitochondrial membrane potential, activation of caspase-like proteases, and DNA cleavage. The aim of this study was to investigate the mechanism of action of glabridin in C. albicans. Materials and Methods: Candida albicans ATCC14053 was applied as the standard strain. Total RNA was extracted from the isolate under glabridin-treated and untreated conditions. To evaluate the alternations in the apoptosis inducing factor (AIF) gene expression, real-time polymerase chain reaction (real-time -PCR) was performed, and the obtained data were analyzed using REST software. Results: Expression of the AIF gene was represented as the ratio of expression relative to the reference gene. According to the REST® output, the expression of the AIF gene increased significantly (P<0.05) under the glabridin-treated condition. Conclusion: Our results suggested that glabridin may induce apoptosis through the caspase-independent route and might be considered as an anti-Candida agent.

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Comparative Evaluation of Antimicrobial Efficacy of Calcium Hydroxide, Chitosan, Chlorhexidine and Their Combinations Against Enterococcus Fecalis and Candida Albicans Using Quantitative Real Time Polymerase Chain Reaction – An In Vitro Study

Advances in Dentistry & Oral Health ◽

10.19080/adoh.2019.11.555817 ◽

2019 ◽

Vol 11 (4) ◽

Author(s):

Archana Srinivasan

Keyword(s):

Polymerase Chain Reaction ◽

Candida Albicans ◽

Calcium Hydroxide ◽

Real Time ◽

Comparative Evaluation ◽

In Vitro Study ◽

Antimicrobial Efficacy ◽

Chain Reaction ◽

Polymerase Chain

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Rapid discrimination between Candida albicans and Candida dubliniensis by using real-time polymerase chain reaction

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2007.01.015 ◽

2007 ◽

Vol 58 (3) ◽

pp. 367-369 ◽

Cited By ~ 13

Author(s):

Ferenc Somogyvari ◽

Ilona Doczi ◽

Julianna Serly ◽

Suhail Ahmad ◽

Elizabeth Nagy

Keyword(s):

Polymerase Chain Reaction ◽

Candida Albicans ◽

Real Time ◽

Candida Dubliniensis ◽

Chain Reaction ◽

Polymerase Chain ◽

Rapid Discrimination

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Molecular diagnosis of Candida albicans using real-time polymerase chain reaction of a CaYST1 gene

Journal of Taibah University for Science ◽

10.1016/s1658-3655(12)60015-6 ◽

2010 ◽

Vol 3 (1) ◽

pp. 8-13 ◽

Cited By ~ 1

Author(s):

Moustafa Y. El-Naggar ◽

Heba M. Al-Basri ◽

Al-Zaharaa A. Karam El-Din

Keyword(s):

Polymerase Chain Reaction ◽

Candida Albicans ◽

Real Time ◽

Molecular Diagnosis ◽

Chain Reaction ◽

Polymerase Chain

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Candida albicans CUG Mistranslation Is a Mechanism To Create Cell Surface Variation

mBio ◽

10.1128/mbio.00285-13 ◽

2013 ◽

Vol 4 (4) ◽

Cited By ~ 51

Author(s):

Isabel Miranda ◽

Ana Silva-Dias ◽

Rita Rocha ◽

Rita Teixeira-Santos ◽

Carolina Coelho ◽

...

Keyword(s):

Candida Albicans ◽

Cell Surface ◽

Fungal Pathogen ◽

Single Gene ◽

Yeast Cells ◽

Phenotypic Switching ◽

Leucine Incorporation ◽

Host Immune System ◽

Content Type ◽

Human Fungal Pathogen

ABSTRACT In the human fungal pathogen Candida albicans, the CUG codon is translated 97% of the time as serine and 3% of the time as leucine, which potentially originates an array of proteins resulting from the translation of a single gene. Genes encoding cell surface proteins are enriched in CUG codons; thus, CUG mistranslation may influence the interactions of the organism with the host. To investigate this, we compared a C. albicans strain that misincorporates 28% of leucine at CUGs with a wild-type parental strain. The first strain displayed increased adherence to inert and host molecules. In addition, it was less susceptible to phagocytosis by murine macrophages, probably due to reduced exposure of cell surface β-glucans. To prove that these phenotypes occurred due to serine/leucine exchange, the C. albicans adhesin and invasin ALS3 was expressed in Saccharomyces cerevisiae in its two natural isoforms (Als3p-Leu and Als3p-Ser). The cells with heterologous expression of Als3p-Leu showed increased adherence to host substrates and flocculation. We propose that CUG mistranslation has been maintained during the evolution of C. albicans due to its potential to generate cell surface variability, which significantly alters fungus-host interactions. IMPORTANCE The translation of genetic information into proteins is a highly accurate cellular process. In the human fungal pathogen Candida albicans, a unique mistranslation event involving the CUG codon occurs. The CUG codon is mainly translated as serine but can also be translated as leucine. Leucine and serine are two biochemically distinct amino acids, hydrophobic and hydrophilic, respectively. The increased rate of leucine incorporation at CUG decoding triggers C. albicans virulence attributes, such as morphogenesis, phenotypic switching, and adhesion. Here, we show that CUG mistranslation masks the fungal cell wall molecule β-glucan that is normally recognized by the host immune system, delaying its response. Furthermore, we demonstrate that two different proteins of the adhesin Als3 generated by CUG mistranslation confer increased hydrophobicity and adhesion ability on yeast cells. Thus, CUG mistranslation functions as a mechanism to create protein diversity with differential activities, constituting an advantage for a mainly asexual microorganism. This could explain its preservation during evolution.

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