Glucose effect on Candida albicans biofilm during tissue invasion

Two strains of Candida albicans were examined for a glucose effect on the catabolism of N-acetylglucosamine. It was shown that the induction of N-acetylglucosamine uptake capacity was almost completely blocked by glucose at 0.5% (w/v), whereas that of N-acetylglucosamine kinase was partially repressed.

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Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approach

PLoS ONE ◽

10.1371/journal.pone.0259588 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0259588

Author(s):

Mohammad Tahseen A. L. Bataineh ◽

Nelson Cruz Soares ◽

Mohammad Harb Semreen ◽

Stefano Cacciatore ◽

Nihar Ranjan Dash ◽

...

Keyword(s):

Candida Albicans ◽

Vital Role ◽

Environmental Cues ◽

Sequencing Analysis ◽

Wild Type ◽

Tissue Invasion ◽

Central Carbon ◽

Life Threatening ◽

Upregulated Genes

Candida albicans is the leading cause of life-threatening bloodstream candidiasis, especially among immunocompromised patients. The reversible morphological transition from yeast to hyphal filaments in response to host environmental cues facilitates C. albicans tissue invasion, immune evasion, and dissemination. Hence, it is widely considered that filamentation represents one of the major virulence properties in C. albicans. We have previously characterized Ppg1, a PP2A-type protein phosphatase that controls filament extension and virulence in C. albicans. This study conducted RNA sequencing analysis of samples obtained from C. albicans wild type and ppg1Δ/Δ strains grown under filament-inducing conditions. Overall, ppg1Δ/Δ strain showed 1448 upregulated and 710 downregulated genes, representing approximately one-third of the entire annotated C. albicans genome. Transcriptomic analysis identified significant downregulation of well-characterized genes linked to filamentation and virulence, such as ALS3, HWP1, ECE1, and RBT1. Expression analysis showed that essential genes involved in C. albicans central carbon metabolisms, including GDH3, GPD1, GPD2, RHR2, INO1, AAH1, and MET14 were among the top upregulated genes. Subsequent metabolomics analysis of C. albicans ppg1Δ/Δ strain revealed a negative enrichment of metabolites with carboxylic acid substituents and a positive enrichment of metabolites with pyranose substituents. Altogether, Ppg1 in vitro analysis revealed a link between metabolites substituents and filament formation controlled by a phosphatase to regulate morphogenesis and virulence.

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Mucosal Tissue Invasion by Candida albicans Is Associated with E-Cadherin Degradation, Mediated by Transcription Factor Rim101p and Protease Sap5p

Infection and Immunity ◽

10.1128/iai.00054-07 ◽

2007 ◽

Vol 75 (5) ◽

pp. 2126-2135 ◽

Cited By ~ 127

Author(s):

C. C. Villar ◽

H. Kashleva ◽

C. J. Nobile ◽

A. P. Mitchell ◽

A. Dongari-Bagtzoglou

Keyword(s):

Candida Albicans ◽

Epithelial Cells ◽

Oral Mucosa ◽

Cell Junctions ◽

Fungal Virulence ◽

Oral Epithelial Cells ◽

Tissue Invasion ◽

Mucosal Tissues ◽

Oral Epithelial ◽

E Cadherin

ABSTRACT The ability of Candida albicans to invade mucosal tissues is a major virulence determinant of this organism; however, the mechanism of invasion is not understood in detail. Proteolytic breakdown of E-cadherin, the major protein in epithelial cell junctions, has been proposed as a mechanism of invasion of certain bacteria in the oral mucosa. The objectives of this study were (i) to assess whether C. albicans degrades E-cadherin expressed by oral epithelial cells in vitro; (ii) to compare the abilities of strains with different invasive potentials to degrade this protein; and (iii) to investigate fungal virulence factors responsible for E-cadherin degradation. We found that while E-cadherin gene expression was not altered, E-cadherin was proteolytically degraded during the interaction of oral epithelial cells with C. albicans. Moreover, C. albicans-mediated degradation of E-cadherin was completely inhibited in the presence of protease inhibitors. Using a three-dimensional model of the human oral mucosa, we found that E-cadherin was degraded in localized areas of tissue invasion by C. albicans. An invasion-deficient rim101 −/rim101 − strain was deficient in degradation of E-cadherin, and this finding suggested that proteases may depend on Rim101p for expression. Indeed, reverse transcription-PCR data indicated that expression of the SAP4, SAP5, and SAP6 genes is severely reduced in the rim101 −/rim101 − mutant. These SAP genes are functional Rim101p targets, because engineered expression of SAP5 in the rim101 −/rim101 − strain restored E-cadherin degradation and invasion in the mucosal model. Our data support the hypothesis that there is a mechanism by which C. albicans invades mucosal tissues by promoting the proteolytic degradation of E-cadherin in epithelial adherens junctions.

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