The effect of subinhibitory concentrations of gentian violet on the germ tube formation by Candida albicans and its adherence to oral epithelial cells

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.

Download Full-text

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

PLoS Pathogens ◽

10.1371/journal.ppat.1009221 ◽

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.

Download Full-text

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

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2730-2 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

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.

Download Full-text

Subinhibitory Concentrations of Triclosan Promote Streptococcus mutans Biofilm Formation and Adherence to Oral Epithelial Cells

PLoS ONE ◽

10.1371/journal.pone.0089059 ◽

2014 ◽

Vol 9 (2) ◽

pp. e89059 ◽

Cited By ~ 27

Author(s):

Telma Blanca Lombardo Bedran ◽

Louis Grignon ◽

Denise Palomari Spolidorio ◽

Daniel Grenier

Keyword(s):

Epithelial Cells ◽

Streptococcus Mutans ◽

Biofilm Formation ◽

Oral Epithelial Cells ◽

Subinhibitory Concentrations ◽

Oral Epithelial

Download Full-text

From Attachment to Damage: Defined Genes of Candida albicans Mediate Adhesion, Invasion and Damage during Interaction with Oral Epithelial Cells

PLoS ONE ◽

10.1371/journal.pone.0017046 ◽

2011 ◽

Vol 6 (2) ◽

pp. e17046 ◽

Cited By ~ 143

Author(s):

Betty Wächtler ◽

Duncan Wilson ◽

Katja Haedicke ◽

Frederic Dalle ◽

Bernhard Hube

Keyword(s):

Candida Albicans ◽

Epithelial Cells ◽

Oral Epithelial Cells ◽

Oral Epithelial

Download Full-text

The effect of secretory immunoglobulin A on the in-vitro adherence of the yeast Candida albicans to human oral epithelial cells

Archives of Oral Biology ◽

10.1016/0003-9969(82)90184-4 ◽

1982 ◽

Vol 27 (8) ◽

pp. 617-621 ◽

Cited By ~ 57

Author(s):

K. Vudhichamnong ◽

D.M. Walker ◽

H.C. Ryley

Keyword(s):

Candida Albicans ◽

Epithelial Cells ◽

Immunoglobulin A ◽

Secretory Immunoglobulin A ◽

Oral Epithelial Cells ◽

Oral Epithelial ◽

Secretory Immunoglobulin

Download Full-text

Interleukin-18 and Gamma Interferon Production by Oral Epithelial Cells in Response to Exposure to Candida albicans or Lipopolysaccharide Stimulation

Infection and Immunity ◽

10.1128/iai.70.12.7073-7080.2002 ◽

2002 ◽

Vol 70 (12) ◽

pp. 7073-7080 ◽

Cited By ~ 65

Author(s):

Mahmoud Rouabhia ◽

Geneviève Ross ◽

Nathalie Pagé ◽

Jamila Chakir

Keyword(s):

Candida Albicans ◽

Epithelial Cells ◽

Early Stage ◽

Oral Candidiasis ◽

Gamma Interferon ◽

Interleukin 18 ◽

Dimorphic Fungus ◽

Oral Epithelial Cells ◽

Ifn Γ ◽

Oral Epithelial

ABSTRACT Oral candidiasis is a collective name for a group of disorders caused by the dimorphic fungus Candida albicans. Host defenses against C. albicans essentially fall into two categories: specific immune mechanisms and local oral mucosal epithelial cell defenses. Since oral epithelial cells secrete a variety of cytokines and chemokines in response to oral microorganisms and since C. albicans is closely associated with oral epithelial cells as a commensal organism, we wanted to determine whether interleukin-18 (IL-18) and gamma interferon (IFN-γ) were produced by oral epithelial cells in response to C. albicans infection and lipopolysaccharide (LPS) stimulation. Our results showed that IL-18 mRNA and protein were constitutively expressed by oral epithelial cells and were down-regulated by Candida infections but increased following LPS stimulation. Both C. albicans and LPS significantly decreased pro-IL-18 (24 kDa) levels and increased active IL-18 (18 kDa) levels. This effect was IL-1β-converting-enzyme dependent. The increase in active IL-18 protein levels promoted the production of IFN-γ by infected cells. No effect was obtained with LPS. Although produced only at an early stage, secreted IFN-γ seemed to be a preferential response by oral epithelial cells to C. albicans growth. These results provide additional evidence for the contribution of oral epithelial cells to local (direct contact) and systemic (IL-18 and IFN-γ production) defense against exogenous stimulation such as C. albicans infection or LPS stimulation.

Download Full-text