scholarly journals Candida albicans Ecm33p Is Important for Normal Cell Wall Architecture and Interactions with Host Cells

2006 ◽  
Vol 5 (1) ◽  
pp. 140-147 ◽  
Author(s):  
Raquel Martinez-Lopez ◽  
Hyunsook Park ◽  
Carter L. Myers ◽  
Concha Gil ◽  
Scott G. Filler
Keyword(s):  
Endothelial Cells ◽  
Cell Wall ◽  
Candida Albicans ◽  
Epithelial Cells ◽  
Normal Cell ◽  
Cell Wall Integrity ◽  
Host Cells ◽  
Epithelial Cell Line ◽  
Oral Epithelial ◽  
Cell Wall Architecture

ABSTRACT Candida albicans ECM33 encodes a glycosylphosphatidylinositol-linked cell wall protein that is important for cell wall integrity. It is also critical for normal virulence in the mouse model of hematogenously disseminated candidiasis. To identify potential mechanisms through which Ecm33p contributes to virulence, we investigated the interactions of C. albicans ecm33Δ mutants with endothelial cells and the FaDu oral epithelial cell line in vitro. The growth rate of blastospores of strains containing either one or no intact copies of ECM33 was 50% slower than that of strains containing two intact copies of ECM33. However, all strains germinated at the same rate, forming similar-length hyphae on endothelial cells and oral epithelial cells. Strains containing either one or no intact copies of ECM33 had modestly reduced adherence to both types of host cells, and a markedly reduced capacity to invade and damage these cells. Saccharomyces cerevisiae expressing C. albicans ECM33 did not adhere to or invade epithelial cells, suggesting that Ecm33p by itself does not act as an adhesin or invasin. Examination of ecm33Δ mutants by transmission electron microscopy revealed that the cell wall of these strains had an abnormally electron-dense outer mannoprotein layer, which may represent a compensatory response to reduced cell wall integrity. The hyphae of these mutants also had aberrant surface localization of the adhesin Als1p. Collectively, these results suggest that Ecm33p is required for normal cell wall architecture as well as normal function and expression of cell surface proteins in C. albicans.

scholarly journals Transcriptional Responses of Candida albicans to Epithelial and Endothelial Cells

2009 ◽  
Vol 8 (10) ◽  
pp. 1498-1510 ◽  
Author(s):  
Hyunsook Park ◽  
Yaoping Liu ◽  
Norma Solis ◽  
Joshua Spotkov ◽  
Jessica Hamaker ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Candida Albicans ◽  
Epithelial Cells ◽  
Multiple Stressors ◽  
Cell Damage ◽  
Host Cells ◽  
Epithelial Cell Line ◽  
Transcriptional Responses ◽  
Oral Epithelial

ABSTRACT Candida albicans interacts with oral epithelial cells during oropharyngeal candidiasis and with vascular endothelial cells when it disseminates hematogenously. We set out to identify C. albicans genes that govern interactions with these host cells in vitro. The transcriptional response of C. albicans to the FaDu oral epithelial cell line and primary endothelial cells was determined by microarray analysis. Contact with epithelial cells caused a decrease in transcript levels of genes related to protein synthesis and adhesion, whereas contact with endothelial cells did not significantly influence any specific functional category of genes. Many genes whose transcripts were increased in response to either host cell had not been previously characterized. We constructed mutants with homozygous insertions in 22 of these uncharacterized genes to investigate their function during host-pathogen interaction. By this approach, we found that YCK2, VPS51, and UEC1 are required for C. albicans to cause normal damage to epithelial cells and resist antimicrobial peptides. YCK2 is also necessary for maintenance of cell polarity. VPS51 is necessary for normal vacuole formation, resistance to multiple stressors, and induction of maximal endothelial cell damage. UEC1 encodes a unique protein that is required for resistance to cell membrane stress. Therefore, some C. albicans genes whose transcripts are increased upon contact with epithelial or endothelial cells are required for the organism to damage these cells and withstand the stresses that it likely encounters during growth in the oropharynx and bloodstream.

scholarly journals The MP65 gene is required for cell wall integrity, adherence to epithelial cells and biofilm formation in Candida albicans

2011 ◽  
Vol 11 (1) ◽  
pp. 106 ◽  
Author(s):  
Silvia Sandini ◽  
Annarita Stringaro ◽  
Silvia Arancia ◽  
Marisa Colone ◽  
Francesca Mondello ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Epithelial Cells ◽  
Biofilm Formation ◽  
Cell Wall Integrity

scholarly journals Candida albicans Secreted Aspartic Protease 7 is Essential for Damage of Human Oral Epithelial Cells

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Yang HP ◽  
◽  
Tsang PCS ◽  
Pow EHN ◽  
Lam OLT ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Mutant Strain ◽  
Tissue Damage ◽  
Wide Spectrum ◽  
Host Cells ◽  
Wild Type ◽  
Oral Epithelial Cells ◽  
Disruption Method ◽  
Oral Epithelial

Aims: Candida albicans is an important human fungal pathogen in clinical settings. It possesses a wide spectrum of virulence traits, including but not limited to the production of Secreted Aspartic Proteases (SAPs), to invade host cells under predisposing conditions. The aims of the present study were to investigate the functional role of C. albicans SAP7 in invasion ability. Methods: The present study was carried out to construct C. albicans sap7Δ/Δ mutant strain using a PCR-based gene disruption method. The behaviors of this SAP7 knockout strain was evaluated and compared with the wild type and SAP7 complemented strains between human oral epithelial cells with respect to endocytosis, invasion, and tissue damage. Results: Compared with the wild type C. albicans strain, a 52% reduction in the endocytosis of the sap7Δ/Δ mutant strain by oral epithelial cells was observed, as well as a 25% attenuation of internalization, and a 27% reduction of tissue damage (P<0.05). Conclusion: Our data clearly demonstrates that C. albicans SAP7 contributes to tissue invasion into human oral epithelial cells which warrant further investigations as potential targets for antifungal interventions.

scholarly journals Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

2015 ◽  
Vol 83 (7) ◽  
pp. 2614-2626 ◽  
Author(s):  
Rohitashw Kumar ◽  
Darpan Saraswat ◽  
Swetha Tati ◽  
Mira Edgerton
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Oral Candidiasis ◽  
Oral Microbiome ◽  
Proteinase Activity ◽  
Adhesion Properties ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
Cell Cell

Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually withC. albicanscells overexpressing Sap6 (SAP6OE and a Δsap8strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6strain was attenuated. These hypervirulent strains had highly aggregative colony structurein vitroand higher secreted proteinase activity; however, the levels of proteinase activity ofC. albicansSaps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6OE and Δsap8cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increasedC. albicansadhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.

scholarly journals UDP-glucose 4, 6-dehydratase Activity Plays an Important Role in Maintaining Cell Wall Integrity and Virulence of Candida albicans

2011 ◽  
Vol 7 (11) ◽  
pp. e1002384 ◽  
Author(s):  
Manimala Sen ◽  
Bhavin Shah ◽  
Srabanti Rakshit ◽  
Vijender Singh ◽  
Bhavna Padmanabhan ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Cell Wall Integrity ◽  
Dehydratase Activity

scholarly journals Activation of EphA2-EGFR signaling in oral epithelial cells by Candida albicans virulence factors

2021 ◽  
Vol 17 (1) ◽  
pp. e1009221
Author(s):  
Marc Swidergall ◽  
Norma V. Solis ◽  
Nicolas Millet ◽  
Manning Y. Huang ◽  
Jianfeng Lin ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Virulence Factors ◽  
Growth Factor Receptor ◽  
Egfr Signaling ◽  
High Concentration ◽  
Oral Epithelial Cells ◽  
Proinflammatory Mediators ◽  
Epidermal Growth ◽  
Oral Epithelial

During oropharyngeal candidiasis (OPC), Candida albicans invades and damages oral epithelial cells, which respond by producing proinflammatory mediators that recruit phagocytes to foci of infection. The ephrin type-A receptor 2 (EphA2) detects β-glucan and plays a central role in stimulating epithelial cells to release proinflammatory mediators during OPC. The epidermal growth factor receptor (EGFR) also interacts with C. albicans and is known to be activated by the Als3 adhesin/invasin and the candidalysin pore-forming toxin. Here, we investigated the interactions among EphA2, EGFR, Als3 and candidalysin during OPC. We found that EGFR and EphA2 constitutively associate with each other as part of a heteromeric physical complex and are mutually dependent for C. albicans-induced activation. Als3-mediated endocytosis of a C. albicans hypha leads to the formation of an endocytic vacuole where candidalysin accumulates at high concentration. Thus, Als3 potentiates targeting of candidalysin, and both Als3 and candidalysin are required for C. albicans to cause maximal damage to oral epithelial cells, sustain activation of EphA2 and EGFR, and stimulate pro-inflammatory cytokine and chemokine secretion. In the mouse model of OPC, C. albicans-induced production of CXCL1/KC and CCL20 is dependent on the presence of candidalysin and EGFR, but independent of Als3. The production of IL-1α and IL-17A also requires candidalysin but is independent of Als3 and EGFR. The production of TNFα requires Als1, Als3, and candidalysin. Collectively, these results delineate the complex interplay among host cell receptors EphA2 and EGFR and C. albicans virulence factors Als1, Als3 and candidalysin during the induction of OPC and the resulting oral inflammatory response.

scholarly journals Determination of the effects of cinnamon bark fractions on Candida albicans and oral epithelial cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Marie-Pier Veilleux ◽  
Daniel Grenier
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Essential Oil ◽  
Biofilm Formation ◽  
Epithelial Barrier ◽  
Cinnamon Oil ◽  
Cinnamon Bark ◽  
Oral Epithelial Cells ◽  
Oral Epithelial

Abstract Background Candida albicans is an opportunistic pathogen that causes oral candidiasis and denture stomatitis. It has also been reported to infect oral mucositis lesions in patients who suffer from cancer affecting the head and neck and who receive chemotherapy and radiotherapy treatments. This study aimed to investigate the effects of two cinnamon bark fractions, i.e., an essential oil and an aqueous extract enriched in proanthocyanidins (Cinnulin PF®) on growth, biofilm formation, and adherence properties of C. albicans as well as on oral epithelial cells (barrier integrity, inflammatory response). Methods A microplate dilution assay was used to determine antifungal and anti-biofilm properties. A fluorescent assay was used to determine C. albicans adherence to oral epithelial cells. Cytotoxicity toward oral epithelial cells was assessed by determination of cell metabolic activity. Tight junction integrity of gingival keratinocytes was assessed by determination of transepithelial electrical resistance. IL-6 and IL-8 secretion by TNFα-stimulated oral epithelial cells was quantified by ELISA. Results While Cinnulin PF® did not reduce C. albicans growth, the cinnamon bark oil exhibited high antifungal activity with minimum inhibitory concentrations and minimum fungicidal concentrations in the range of 0.039 to 0.078%. The cinnamon oil was also active against a pre-formed C. albicans biofilm. Interestingly, Cinnulin PF® prevented biofilm formation by C. albicans and attenuated its adherence to oral epithelial cells. At their effective concentrations, the cinnamon oil and the Cinnulin PF® displayed no significant cytotoxicity against oral epithelial cells. In an in vitro model, both cinnamon fractions reinforced the integrity of the oral epithelial barrier. Lastly, Cinnulin PF® inhibited the secretion of interleukin-6 and interleukin-8 by oral epithelial cells stimulated with TNF-α. Conclusion By their ability to attenuate growth, biofilm formation and adherence property of C. albicans, to reinforce the epithelial barrier function, and to exert anti-inflammatory properties the two cinnamon fractions (essential oil, Cinnulin PF®) investigated in the present study may be promising agents for treating oral infections involving C. albicans.

scholarly journals Invasive Phenotype of Candida albicans Affects the Host Proinflammatory Response to Infection

2005 ◽  
Vol 73 (8) ◽  
pp. 4588-4595 ◽  
Author(s):  
C. C. Villar ◽  
H. Kashleva ◽  
A. P. Mitchell ◽  
A. Dongari-Bagtzoglou
Keyword(s):  
Endothelial Cells ◽  
Candida Albicans ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Inflammatory Responses ◽  
Gene Knockout ◽  
Critical Role ◽  
Host Cells ◽  
Proinflammatory Response ◽  
Cytokine Responses

ABSTRACT Candida albicans is a major opportunistic pathogen in immunocompromised patients. Production of proinflammatory cytokines by host cells in response to C. albicans plays a critical role in the activation of immune cells and final clearance of the organism. Invasion of host cells and tissues is considered one of the virulence attributes of this organism. The purpose of this study was to investigate whether the ability of C. albicans to invade host cells and tissues affects the proinflammatory cytokine responses by epithelial and endothelial cells. In this study we used the invasion-deficient RIM101 gene knockout strain DAY25, the highly invasive strain SC5314, and highly invasive RIM101-complemented strain DAY44 to compare the proinflammatory cytokine responses by oral epithelial or endothelial cells. Using a high-throughput approach, we found both qualitative and quantitative differences in the overall inflammatory responses to C. albicans strains with different invasive potentials. Overall, the highly invasive strains triggered higher levels of proinflammatory cytokines in host cells than the invasion-deficient mutant triggered. Significant differences compared to the attenuated mutant were noted in interleukin-1α (IL-1α), IL-6, IL-8, and tumor necrosis factor alpha in epithelial cells and in IL-6, growth-related oncogene, IL-8, monocyte chemoattractant protein 1 (MCP-1), MCP-2, and granulocyte colony-stimulating factor in endothelial cells. Our results indicate that invasion of host cells and tissues by C. albicans enhances the host proinflammatory response to infection.

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