Cranberry proanthocyanidins inhibit the adherence properties of Candida albicans and cytokine secretion by oral epithelial cells

Candida albicans is known as a commensal microorganism but it is also the most common fungal pathogen in humans, causing both mucosal and systemic infections. Biofilm-associated C. albicans infections present clinically important features due to their high levels of resistance to traditional antifungal agents. Quorum sensing is closely associated with biofilm formation and increasing fungal pathogenicity. We investigated the ability of the novel bacterial quorum sensing quencher thiazolidinedione-8 (S-8) to inhibit the formation of, and eradication of mature C. albicans biofilms. In addition, the capability of S-8 to alter fungal adhesion to mammalian cells was checked. S-8 exhibited specific antibiofilm and antiadhesion activities against C. albicans, at four- to eightfold lower concentrations than the minimum inhibitory concentration (MIC). Using fluorescence microscopy, we observed that S-8 dose-dependently reduces C. albicans–GFP binding to RAW macrophages. S-8 at sub-MICs also interfered with fungal morphogenesis by inhibiting the yeast-to-hyphal form transition. In addition, the tested agent strongly affected fungal cell wall characteristics by modulating its hydrophobicity. We evaluated the molecular mode of S-8 antibiofilm and antiadhesion activities using real-time RT-PCR. The expression levels of genes associated with biofilm formation, adhesion and filamentation, HWP1, ALS3 and EAP1, respectively, were dose-dependently downregulated by S-8. Transcript levels of UME6, responsible for long-term hyphal maintenance, were also significantly decreased by the tested agent. Both signaling pathways of hyphal formation-cAMP-PKA and MAPK-were interrupted by S-8. Their upstream general regulator RAS1 was markedly suppressed by S-8. In addition, the expression levels of MAPK cascade components CST20, HST7 and CPH1 were downregulated by S-8. Finally, transcriptional repressors of filament formation, TUP1 and NRG1, were dramatically upregulated by our compound. Our results indicate that S-8 holds a novel antibiofilm therapeutic mean in the treatment and prevention of biofilm-associated C. albicans infections.

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“…One venue is developing novel agents interfering with biofilm formation [24]–[26] not necessarily affecting viability of the Candida.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Thiazolidinedione-8 as an Antibiofilm Agent against Candida albicans

et al. 2014

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“…SRMs with the concentrations of S-8 described above were placed in a 12-well polystyrene microplate (Thermo Scientific) and incubated with C. albicans in RPMI medium for 48 h at 37°C. Then, the SRMs were removed from the wells, and the biofilm formed next to the membrane was washed with PBS, followed by staining with 0.02% crystal violet for 45 min (25). The wells were washed with PBS to remove residual crystal violet and dried overnight at room temperature.…”

Section: Synthesis Of S-8mentioning

confidence: 99%

Sustained Release of a Novel Anti-Quorum-Sensing Agent against Oral Fungal Biofilms

Feldman

Shenderovich

Al-Quntar

et al. 2015

Antimicrob Agents Chemother

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b Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against Candida albicans biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature C. albicans biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases.

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“…The presence of polyphenols and organic acids was also confirmed by LC-MS. Other compounds detected during the analysis were ferulic acid, gallic acids, chlorogenic and neochlorogenic acids, quercetin-3-rhamnoside, quercetin-3glucuronide, quercetin-3-benzylogalactoside, and methylquercetin-3-xyloside. We also detected type A proanthocyanidins, which are responsible for antiadhesive properties of V. macrocarpon (5,9). Figures 2 and 3 present the results of adhesion studies after 6 days of incubation.…”

Section: Resultsmentioning

confidence: 88%

Adhesion of Asaia bogorensis to Glass and Polystyrene in the Presence of Cranberry Juice

Antolak

Kręgiel

Czyżowska

2015

Journal of Food Protection

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The aim of the study was to evaluate the adhesion abilities of the acetic acid bacterium Asaia bogorensis to glass and polystyrene in the presence of American cranberry (Vaccinium macrocarpon) juice. The strain of A. bogorensis used was isolated from spoiled commercial fruit-flavored drinking water. The cranberry juice was analyzed for polyphenols, organic acids, and carbohydrates using high-performance liquid chromatography and liquid chromatography-mass spectrometry techniques. The adhesive abilities of bacterial cells in culture medium supplemented with cranberry juice were determined using luminometry and microscopy. The viability of adhered and planktonic bacterial cells was determined by the plate count method, and the relative adhesion coefficient was calculated. This strain of A. bogorensis was characterized by strong adhesion properties that were dependent upon the type of surface. The highest level of cell adhesion was found on the polystyrene. However, in the presence of 10% cranberry juice, attachment of bacterial cells was three times lower. Chemical analysis of juice revealed the presence of sugars, organic acids, and anthocyanins, which were identified as galactosides, glucosides, and arabinosides of cyanidin and peonidin. A-type proanthocyanidins responsible for the antiadhesion properties of V. macrocarpon also were detected.

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Cranberry proanthocyanidins inhibit the adherence properties of Candida albicans and cytokine secretion by oral epithelial cells

Cited by 63 publications

References 56 publications

Therapeutic Potential of Thiazolidinedione-8 as an Antibiofilm Agent against Candida albicans

Therapeutic Potential of Thiazolidinedione-8 as an Antibiofilm Agent against Candida albicans

Sustained Release of a Novel Anti-Quorum-Sensing Agent against Oral Fungal Biofilms

Adhesion of Asaia bogorensis to Glass and Polystyrene in the Presence of Cranberry Juice

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