Effect of pepstatin A on the virulence factors of Candida albicans strains isolated from vaginal environment of patients in three different clinical conditions

Candida albicans lives as commensal on the skin and mucosal surfaces of the genital, intestinal, vaginal, urinary, and oral tracts of 80% of healthy individuals [...]

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Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and ReducesIn VivoPathogenicity

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01451-12 ◽

2012 ◽

Vol 57 (1) ◽

pp. 445-451 ◽

Cited By ~ 41

Author(s):

Ilka Tiemy Kato ◽

Renato Araujo Prates ◽

Caetano Padial Sabino ◽

Beth Burgwyn Fuchs ◽

George P. Tegos ◽

...

Keyword(s):

Candida Albicans ◽

Virulence Factors ◽

Sodium Dodecyl ◽

Systemic Infection ◽

Tube Formation ◽

Photodynamic Inactivation ◽

Content Type ◽

Daughter Cells

ABSTRACTThe objective of this study was to evaluate whetherCandida albicansexhibits altered pathogenicity characteristics following sublethal antimicrobial photodynamic inactivation (APDI) and if such alterations are maintained in the daughter cells.C. albicanswas exposed to sublethal APDI by using methylene blue (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (λ 660 nm, 75 mW/cm2, 9 to 27 J/cm2).In vitro, we evaluated APDI effects onC. albicansgrowth, germ tube formation, sensitivity to oxidative and osmotic stress, cell wall integrity, and fluconazole susceptibility.In vivo, we evaluatedC. albicanspathogenicity with a mouse model of systemic infection. Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the growth rate and the ability ofC. albicansto form germ tubes compared to untreated cells (P< 0.05). Survival of mice systemically infected withC. albicanspretreated with APDI was significantly increased compared to mice infected with untreated yeast (P< 0.05). APDI increasedC. albicanssensitivity to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for fluconazole forC. albicanswas also reduced following sublethal MB-mediated APDI. However, none of those pathogenic parameters was altered in daughter cells ofC. albicanssubmitted to APDI. These data suggest that APDI may inhibit virulence factors and reducein vivopathogenicity ofC. albicans. The absence of alterations in daughter cells indicates that APDI effects are transitory. The MIC reduction for fluconazole following APDI suggests that this antifungal could be combined with APDI to treatC. albicansinfections.

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The Inflammatory Response Induced by Aspartic Proteases of Candida albicans Is Independent of Proteolytic Activity

Infection and Immunity ◽

10.1128/iai.00789-10 ◽

2010 ◽

Vol 78 (11) ◽

pp. 4754-4762 ◽

Cited By ~ 35

Author(s):

Donatella Pietrella ◽

Anna Rachini ◽

Neelam Pandey ◽

Lydia Schild ◽

Mihai Netea ◽

...

Keyword(s):

Candida Albicans ◽

Inflammatory Response ◽

Proteolytic Activity ◽

Necrosis Factor Alpha ◽

Pathogenic Yeast ◽

Aspartic Proteases ◽

Akt Activation ◽

Tnf Α ◽

Factor Alpha ◽

Pepstatin A

ABSTRACT The secretion of aspartic proteases (Saps) has long been recognized as a virulence-associated trait of the pathogenic yeast Candida albicans. In this study, we report that different recombinant Saps, including Sap1, Sap2, Sap3, and Sap6, have differing abilities to induce secretion of proinflammatory cytokines by human monocytes. In particular Sap1, Sap2, and Sap6 significantly induced interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 production. Sap3 was able to stimulate the secretion of IL-1β and TNF-α. All Saps tested were able to induce Ca2+ influx in monocytes. Treatment of these Saps with pepstatin A did not have any effect on cytokine secretion, indicating that their stimulatory potential was independent from their proteolytic activity. The capacity of Saps to induce inflammatory cytokine production was also independent from protease-activated receptor (PAR) activation and from the optimal pH for individual Sap activity. The interaction of Saps with monocytes induced Akt activation and phosphorylation of IκBα, which mediates translocation of NF-κB into the nucleus. Overall, these results suggest that individual Sap proteins can induce an inflammatory response and that this phenomenon is independent from the pH of a specific host niche and from Sap enzymatic activity. The inflammatory response is partially dependent on Sap denaturation and is triggered by the Akt/NF-κB activation pathway. Our data suggest a novel, activity-independent aspect of Saps during interactions of C. albicans with the host.

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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.

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Germ Tubes and Proteinase Activity Contribute to Virulence of Candida albicans in Murine Peritonitis

Infection and Immunity ◽

10.1128/iai.67.12.6637-6642.1999 ◽

1999 ◽

Vol 67 (12) ◽

pp. 6637-6642 ◽

Cited By ~ 56

Author(s):

Marianne Kretschmar ◽

Bernhard Hube ◽

Thomas Bertsch ◽

Dominique Sanglard ◽

Renate Merker ◽

...

Keyword(s):

Candida Albicans ◽

Bowel Perforation ◽

Tube Length ◽

Triple Mutant ◽

Liver And Pancreas ◽

Organ Specific ◽

Secreted Aspartyl Proteinase ◽

Pepstatin A

ABSTRACT Peritonitis with Candida albicans is an important complication of bowel perforation and continuous ambulatory peritoneal dialysis. To define potential virulence factors, we investigated 50 strains of C. albicans in a murine peritonitis model. There was considerable variation in their virulence in this model when virulence was measured as release of organ-specific enzymes into the plasma of infected mice. Alanine aminotransferase (ALT) and α-amylase (AM) were used as parameters for damage of the liver and pancreas, respectively. The activities of ALT and AM in the plasma correlated with invasion into the organs measured in histologic sections and the median germ tube length induced with serum in vitro. When the activity of proteinases was inhibited in vivo with pepstatin A, there was a significant reduction of ALT and AM activities. This indicates that proteinases contributed to virulence in this model. Using strains ofC. albicans with disruption of secreted aspartyl proteinase gene SAP1, SAP2, SAP3, orSAP4 through SAP6 (collectively referred to asSAP4-6), we showed that only a Δsap4-6 triple mutant induced a significantly reduced activity of ALT in comparison to the reference strain. In contrast to the Δsap1, Δsap2, and Δsap3 mutants, the ALT induced by the Δsap4-6 mutant could not be further reduced by pepstatin A treatment, which indicates that Sap4-6 may contribute to virulence in this model.

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Virulence Factor and Pathogenicity of Candida albicans in Oral Candidiasis

World Journal of Dentistry ◽

10.5005/jp-journals-10015-1243 ◽

2013 ◽

Vol 4 (4) ◽

pp. 267-271 ◽

Cited By ~ 4

Author(s):

Abdillah Imron Nasution

Keyword(s):

Antibiotic Resistance ◽

Candida Albicans ◽

Immune System ◽

Virulence Factors ◽

Virulence Factor ◽

Oral Candidiasis ◽

Complex Process ◽

Phenotype Switching

ABSTRACT Candida albicans is an opportunistic fungus causing various forms of candidiasis. However, under certain circumstances it is capable of becoming pathogenic. Pathogenicity of oral candidiasis is a complex process and there is no one factor that can be regarded as the direct cause. This review aims to explain the virulence factors of Candida albicans in oral candidiasis infection and its relation to homeostasis in the mouth. Virulence factors of Candida albicans which is closely related to the nature of pathogens include: adherence and coaggregation, interference of immune system, phenotype switching and several supporting factors such as antibiotic resistance and immunomodulating. How to cite this article Nasution AI. Virulence Factor and Pathogenicity of Candida albicans in Oral Candidiasis. World J Dent 2013;4(4):267-271.

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Paeonol assists fluconazole and amphotericin B to inhibit virulence factors and pathogenicity of Candida albicans

Biofouling ◽

10.1080/08927014.2021.1985473 ◽

2021 ◽

pp. 1-16

Author(s):

Min Pan ◽

Qirui Wang ◽

Ting Cheng ◽

Daqiang Wu ◽

Tianming Wang ◽

...

Keyword(s):

Candida Albicans ◽

Amphotericin B ◽

Virulence Factors

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Impact of serial systemic infection on Candida albicans virulence factors

Future Microbiology ◽

10.2217/fmb-2019-0342 ◽

2020 ◽

Vol 15 (13) ◽

pp. 1249-1263

Author(s):

Glaucia S Arita ◽

Daniella R Faria ◽

Karina M Sakita ◽

Franciele AV Rodrigues-Vendramini ◽

Isis RG Capoci ◽

...

Keyword(s):

Candida Albicans ◽

Virulence Factors ◽

Murine Model ◽

Systemic Infection ◽

Systemic Candidiasis ◽

Fungal Burden ◽

Histopathological Findings ◽

Phenotypic Profile ◽

Proteomic Data ◽

Repeated Contact

Aim: To evaluate changes in virulence and pathogenicity approaches from Candida albicans after successive passages in a murine model of systemic candidiasis. Materials & methods: Phenotypic assays were performed using colonies recovered from animals infected serially, totalizing five passages. Results: A progressive infection was observed along the passages, with increased fungal burden and the presence of greater inflammatory areas in the histopathological findings. Recovered strains exhibited increased filamentation and biofilm abilities, along with modulation of phospholipase and proteinase activities. Conclusion: Repeated contact between yeast and host increased the expression of virulence factors. Furthermore, a correspondence between phenotypic profile and proteomic data obtained previously was observed.

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