Differential humoral response against alpha- and beta-linked mannose residues associated with tissue invasion by Candida albicans.

SUMMARY The cell wall of Candida albicans not only is the structure in which many biological functions essential for the fungal cells reside but also is a significant source of candidal antigens. The major cell wall components that elicit a response from the host immune system are proteins and glycoproteins, the latter being predominantly mannoproteins. Both the carbohydrate and protein moieties are able to trigger immune responses. Although cell-mediated immunity is often considered to be the most important line of defense against candidiasis, cell wall protein and glycoprotein components also elicit a potent humoral response from the host that may include some protective antibodies. Proteins and glycoproteins exposed at the most external layers of the wall structure are involved in several types of interactions of fungal cells with the exocellular environment. Thus, coating of fungal cells with host antibodies has the potential to influence profoundly the host-parasite interaction by affecting antibody-mediated functions such as opsonin-enhanced phagocytosis and blocking the binding activity of fungal adhesins for host ligands. In this review, the various members of the protein and glycoprotein fraction of the C. albicans cell wall that elicit an antibody response in vivo are examined. Although a number of proteins have been shown to stimulate an antibody response, for some of these species the response is not universal. On the other hand, some of the studies demonstrate that certain cell wall antigens and anti-cell wall antibodies may be the basis for developing specific and sensitive serologic tests for the diagnosis of candidasis, particularly the disseminated form. In addition, recent studies have focused on the potential for antibodies to cell wall protein determinants to protect the host against infection. Hence, a better understanding of the humoral response to cell wall antigens of C. albicans may provide the basis for the development of (i) effective procedures for the serodiagnosis of disseminated candidiasis and (ii) novel prophylactic (vaccination) and therapeutic strategies for the management of this type of infection.

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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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Glucose effect on Candida albicans biofilm during tissue invasion

Archives of Oral Biology ◽

10.1016/j.archoralbio.2020.104728 ◽

2020 ◽

Vol 117 ◽

pp. 104728 ◽

Cited By ~ 1

Author(s):

Louise Morais Dornelas Figueira ◽

Antônio Pedro Ricomini Filho ◽

Wander José da Silva ◽

Altair Antoninha Del BeL Cury ◽

Karina Gonzales Silvério Ruiz

Keyword(s):

Candida Albicans ◽

Glucose Effect ◽

Tissue Invasion

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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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