Susceptibility of Candida biofilms to histatin 5 and fluconazole

Konopka, Krystyna; Dorocka‐Bobkowska, Barbara; Gebremedhin, Senait; Düzgüneş, Nejat

doi:10.1007/s10482-010-9417-5

Cited by 36 publications

(32 citation statements)

References 26 publications

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“…Therefore, we also evaluated the viability of biofilms treated with combinations of fluconazole and NO-ASA. Based on reports from similar in vitro studies regarding effective concentrations of fluconazole against biofilms [20,31], we used fluconazole at serial dilutions ranging from 1000 μg/mL to 15,625 μg/mL. Using the checkerboard method, fluconazole was combined with NO-ASA at concentrations ranging from 1 mM to 15.6 μM.…”

Section: Resultsmentioning

confidence: 99%

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

et al. 2017

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Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20–30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 μM NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 μM NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 μM to 700 μM), consistent with SEM findings of altered biofilm microarchitecture. PGE2 and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans.

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Section: Resultsmentioning

confidence: 99%

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

et al. 2017

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“…4A). The concentrations of the peptides causing 50% reduction in the metabolic activity (50% RMA) of the cells were also calculated as previously described (24). The 50% RMAs of P-113, P-113Du, and P-113Tri were Ͼ300, 51.54, and 43.245 g/ml, respectively.…”

Section: Figmentioning

confidence: 99%

The Antimicrobial Peptides P-113Du and P-113Tri Function against Candida albicans

Lin

Chen

Xue

et al. 2016

Antimicrob Agents Chemother

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Two antimicrobial P-113 peptide derivatives, P-113Du and P-113Tri, were investigated in this study. Notably, P-113Du and P-113Tri contained significant fractions of ␣-helix conformation and were less sensitive to high salt and low pH than P-113. Moreover, compared to P-113, these peptides exhibited increased antifungal activity against planktonic cells, biofilm cells, and clinical isolates of Candida albicans and non-albicans Candida spp. These results suggest that P-113Du and P-113Tri are promising candidates for development as novel antifungal agents. Histatin 5 (Hst5) is a potent antimicrobial peptide (AMP) with activity against Candida albicans (1). A 12-mer amino acid fragment of Hst5, P-113, retains strong candidacidal activity compared to the parental Hst5 and has had no adverse effects in clinical trials (2-6). P-113 forms an amphipathic ␣-helix in trifluoroethanol, which mimics the hydrophobic environment of microbial membranes (7). However, the interaction between AMPs and microbial membranes is salt sensitive (8, 9). The efficacy of P-113 is significantly reduced in the presence of high salt concentrations, such as 150 mM sodium chloride or 100 mM sodium phosphate (4, 10).To improve the activity of P-113, our approach was based on the dimerization of histatin-derived peptides to increase bactericidal activity against Staphylococcus aureus (11). In this study, the duplicated and triplicated P-113 (designated P-113Du and P-113Tri, respectively) ( Table 1) were characterized. The secondary structures of the peptides in 85% trifluoroethanol (pH 6.0) were analyzed using an AVIV circular dichroism spectrometer at 25°C. Spectra were measured from 195 to 260 nm at 1-nm intervals, and mean residue molar ellipticity (MRE) was used to compare different peptides. Figure 1 shows an ␣-helical conformation characterized by a strong positive band at 195 nm and two negative bands at 208 and approximately 222 nm (12). The ␣-helical content of P-113 was estimated to be 2.9% using the ␤-structure selection (BeStSel) method (13). However, the ␣-helical contents of P-113Du and P-113Tri were 10.6% and 21.4%, respectively, suggesting the presence of a significant fraction of ␣-helix conformation.To examine the salt sensitivity of the peptides, spot assays were performed ( Fig. 2A). Cells (4.0 ϫ 10 5 cells) of the C. albicans strain SC5314 were incubated with different concentrations of sodium acetate (NaOAc) and peptides for 1 h. The mixtures were then spotted onto 1% yeast extract-2% peptone-2% glucose (YPD) agar. After 24 h of incubation, P-113 exhibited candidacidal activity in the presence of 12.5 mM sodium acetate but reduced activity in the presence of 62.25 and 93.75 mM salt. However, P-113Du and P-113Tri exhibited potent candidacidal activity even in the presence of 93.75 mM sodium acetate ( Fig. 2A). In addition, a previous study indicated that P-113 loses its bactericidal activity at pH 4.5 (14). Therefore, the pH sensitivities of the peptides were examined. P-113 exhibited candidacidal activity at pH 6 and 8, and...

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“…Histatin 5 was described to have antibiofilm activity against biofilms of C. albicans and C. glabrata to a lesser extent [101] and talactoferrin (human recombinant lactoferrin) against biofilms of C. albicans [102].…”

Section: Novel Ros-inducing Antifungal Agentsmentioning

confidence: 99%

Reactive Oxygen Species-Inducing Antifungal Agents and Their Activity Against Fungal Biofilms

2013

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Invasive fungal infections are associated with very high mortality rates ranging from 20-90% for opportunistic fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Fungal resistance to antimycotic treatment can be genotypic (due to resistant strains) as well as phenotypic (due to more resistant fungal lifestyles, such as biofilms). With regard to the latter, biofilms are considered to be critical in the development of invasive fungal infections. However, there are only very few antimycotics, such as miconazole (azoles), echinocandins and liposomal formulations of amphotericin B (polyenes), which are also effective against fungal biofilms. Interestingly, these antimycotics all induce reactive oxygen species (ROS) in fungal (biofilm) cells. This review provides an overview of the different classes of antimycotics and novel antifungal compounds that induce ROS in fungal planktonic and biofilm cells. Moreover, different strategies to further enhance the antibiofilm activity of such ROS-inducing antimycotics will be discussed.

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Susceptibility of Candida biofilms to histatin 5 and fluconazole

Cited by 36 publications

References 26 publications

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

The Antimicrobial Peptides P-113Du and P-113Tri Function against Candida albicans

Reactive Oxygen Species-Inducing Antifungal Agents and Their Activity Against Fungal Biofilms

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