scholarly journals Quercetin Assists Fluconazole to Inhibit Biofilm Formations of Fluconazole-Resistant Candida Albicans in In Vitro and In Vivo Antifungal Managements of Vulvovaginal Candidiasis

2016 ◽  
Vol 40 (3-4) ◽  
pp. 727-742 ◽  
Author(s):  
Mei Gao ◽  
Hui Wang ◽  
LiJuan Zhu
Keyword(s):  
Candida Albicans ◽  
Cell Surface Hydrophobicity ◽  
Surface Hydrophobicity ◽  
Vulvovaginal Candidiasis ◽  
Vaginal Mucosa ◽  
Fluconazole Resistant ◽  
Dietary Flavonoid ◽  
Fungal Adherence

Background: Vulvovaginal candidiasis (VVC) is a common gynecological disease. Candida albicans is believed to be mainly implicated in VVC occurrence, the biofilm of which is one of the virulence factors responsible for resistance to traditional antifungal agents especially to fluconazole (FCZ). Quercetin (QCT) is a dietary flavonoid and has been demonstrated to be antifungal against C. albicans biofilm. Methods: 17 C. albicans isolates including 15 clinical ones isolated from VVC patients were employed to investigate the effects of QCT and/or FCZ on the inhibition of C. albicans biofilm. Results: We observed that 64 µg/mL QCT and/or 128 µg/mL FCZ could (i) be synergistic against 10 FCZ-resistant planktonic and 17 biofilm cells of C. albicans, (ii) inhibit fungal adherence, cell surface hydrophobicity (CSH), flocculation, yeast-to-hypha transition, metabolism, thickness and dispersion of biofilms; (iii) down-regulate the expressions of ALS1, ALS3, HWP1, SUN41, UME6 and ECE1 and up-regulate the expressions of PDE2, NRG1 and HSP90, and we also found that (iv) the fungal burden was reduced in vaginal mucosa and the symptoms were alleviated in a murine VVC model after the treatments of 5 mg/kg QCT and/or 20 mg/kg FCZ. Conclusion: Together with these results, it could be demonstrated that QCT could be a favorable antifungal agent and a promising synergist with FCZ in the clinical management of VVC caused by C. albicans biofilm.

scholarly journals Preclinical approaches in vulvovaginal candidiasis treatment with mucoadhesive thermoresponsive systems containing propolis

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243197
Author(s):  
Amanda Pohlmann Bonfim ◽  
Karina Mayumi Sakita ◽  
Daniella Renata Faria ◽  
Glaucia Sayuri Arita ◽  
Franciele Abigail Vilugron Rodrigues Vendramini ◽  
...  
Keyword(s):  
Vulvovaginal Candidiasis ◽  
Fungal Resistance ◽  
Vaginal Mucosa ◽  
Childbearing Age ◽  
Propolis Extract ◽  
Low Toxicity ◽  
Fluconazole Resistant ◽  
Pharmaceutical Properties

Vulvovaginal candidiasis (VVC) is a common vaginitis that affects women, especially in childbearing age, caused by Candida albicans in almost 80% of cases. Considering the limited drug arsenal available and the increasing fungal resistance profile, the search for new therapeutic sources with low toxicity and easy administration should be supported. Propolis has been used as a traditional medicine for multiple diseases, considering its particular composition and pharmaceutical properties that permits its wide applicability; it has also emerged as a potential antifungal agent. Thus, this study performed an in vitro and in vivo investigation into the efficacy of a new mucoadhesive thermoresponsive platform for propolis delivery (MTS-PRPe) in a preclinical murine model of VVC treatment caused by C. albicans. The methodologies involved chemical analysis, an assessment of the rheological and mucoadhesive properties of propolis formulations, in vitro and in vivo antifungal evaluations, histological evaluations and electron microscopy of the vaginal mucosa. The results demonstrated the antifungal activity of propolis extract and MTS-PRP against the standard strain and a fluconazole-resistant clinical isolate of C. albicans, in both in vitro and in vivo assays. These results were similar and even better, depending on the propolis concentration, when compared to nystatin. Thus, the formulation containing propolis exhibited good performance against C. albicans in a vulvovaginal candidiasis experimental model, representing a promising opportunity for the treatment of this infection.

Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis

2021 ◽  
Author(s):  
Rodrigo L Fabri ◽  
Jhamine C O Freitas ◽  
Ari S O Lemos ◽  
Lara M Campos ◽  
Irley O M Diniz ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Cell Membrane ◽  
Multidrug Resistant ◽  
Fungal Strain ◽  
Vulvovaginal Candidiasis ◽  
Biofilm Matrix

Abstract Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remains to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. Lay Abstract This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.

scholarly journals Antifungal activity of Ocimum gratissimum L., Lantana camara L. & Pteleopsis suberosa Engl. & Dies used in the treatment of vulvovaginal candidiasis in Benin

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jean Robert Klotoe ◽  
Brice Armand Fanou ◽  
Eric Agbodjento ◽  
Arnaud Houehou ◽  
Lauris Fah ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Aqueous Extract ◽  
Lantana Camara ◽  
Vulvovaginal Candidiasis ◽  
Reference Drug ◽  
Clinical Strains ◽  
Ocimum Gratissimum

Abstract Background Vulvovaginal candidiasis is a widespread mycotic infection that affects a large proportion of women of childbearing age. Its management in traditional medicine is based on the use of medicinal plants. This study aimed to evaluate the antifungal activity of Ocimum gratissimum L., Lantana camara L. and Pteleopsis suberosa Engl. & Diels used in the treatment of vulvovaginal candidiasis in Benin. Results The data obtained from the in vitro antifungal test show that the strains tested (ATCC 90028 and two clinical strains: 1MA and 3MA) were more sensitive to aqueous extracts with a better effect for Pteleopsis suberosa. This potential of the tested extracts correlated with their richness in total polyphenols. The extract of the Pteleopsis suberosa was very active on the inhibition of the reference strain ATCC 90028. On the clinical strains (1MA and 3MA) the aqueous extract of Pteleopsis suberosa showed a better MIC on the 1MA strain. In vivo model, inoculation of 100 µL of the concentrated Candida albicans suspension 1.5 × 105 UFC/mL induced the candidiasis of the female Wistar rat. The treatment with the aqueous extract of Pteleopsis suberosa, like fluconazole (reference drug), significantly reduced Candida albicans infection at a dose of 100 mg/kg after 1, 7 and 13 days of treatment. Conclusion This study revealed the potential antifungal of the Ocimum gratissimum, Lantana camara and Pteleopsis suberosa. Pteleopsis suberosa has better antifungal activity in vitro and in vivo. These observations justify the use of their medicinal plant in the traditional treatment of vulvovaginal candidiasis in Benin.

scholarly journals EVALUATION OF PROBITOIC POTENTIAL OF LACTOBACILLUS STRAINS FROM FERMENTED FOODS AND FEACES OF INFANTS

2016 ◽  
Vol 54 (5) ◽  
pp. 632
Author(s):  
Nguyen Thi My Le ◽  
Nguyen Thi Huong
Keyword(s):  
Cell Surface ◽  
Cell Surface Hydrophobicity ◽  
Acid Tolerance ◽  
Inhibition Zone ◽  
Surface Hydrophobicity ◽  
Salmonella Typhi ◽  
Fermented Foods ◽  
Probiotic Properties

Lactobacillus strains are a major part of the probiotics, microflora of the intestine and of fermented foods. The aim of this study was to evaluate the potential probiotics of six Lactobacillus strains (L. fermentum 39-183; L. plantarum subsp.plantarum P-8; L. casei ATCC 334; L. rhamnosus ATCC 8530, L. brevis KB 290 and L. fermentum JMC 7776). Probiotic properties such as acid tolerance, bile resistance, bacteriocin-like activity, cell surface hydrophobicity and antibiotic resistance were assessed. In vitro results obtained showed that all Lactobacillus strains tested were able to meet the basic requirements for probiotic functions as they demonstrated probiotic characteristics such as tolerance to pH 2.0 and 2% bile salt. All Lactobacillus strains inhibited the growth of E. coli, Staphylococcus aureus and Salmonella Typhi. Among strains tested, L. plantarum subsp.plantarum P-8 showing inhibitory is very promising with inhibition zone ranging between 6.5 to 12.7 mm. The results for cell surface hydrophobicity and susceptibility against antibiotics also showed that L. fermentum JMC 7776 and L. plantarum subsp.plantarum P-8 had higher cell surface hydrophobicity than the rests.  All Lactobacillus tested were resistant to vancomycin and susceptible to streptomycin. The results obtained in this investigation will be used to select potentially probiotic strains for in vivo study

scholarly journals Histological assessment, anti-quorum sensing, and anti-biofilm activities of Dioon spinulosum extract: in vitro and in vivo approach

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Engy Elekhnawy ◽  
Walaa A. Negm ◽  
Mona El-Aasr ◽  
Amal Abo Kamer ◽  
Mohammed Alqarni ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Cell Surface Hydrophobicity ◽  
Fibroblast Cell ◽  
Surface Hydrophobicity ◽  
Human Skin Fibroblast ◽  
Electron Microscopes

AbstractPseudomonas aeruginosa is an opportunistic bacterium causing several health problems and having many virulence factors like biofilm formation on different surfaces. There is a significant need to develop new antimicrobials due to the spreading resistance to the commonly used antibiotics, partly attributed to biofilm formation. Consequently, this study aimed to investigate the anti-biofilm and anti-quorum sensing activities of Dioon spinulosum, Dyer Ex Eichler extract (DSE), against Pseudomonas aeruginosa clinical isolates. DSE exhibited a reduction in the biofilm formation by P. aeruginosa isolates both in vitro and in vivo rat models. It also resulted in a decrease in cell surface hydrophobicity and exopolysaccharide quantity of P. aeruginosa isolates. Both bright field and scanning electron microscopes provided evidence for the inhibiting ability of DSE on biofilm formation. Moreover, it reduced violacein production by Chromobacterium violaceum (ATCC 12,472). It decreased the relative expression of 4 quorum sensing genes (lasI, lasR, rhlI, rhlR) and the biofilm gene (ndvB) using qRT-PCR. Furthermore, DSE presented a cytotoxic activity with IC50 of 4.36 ± 0.52 µg/ml against human skin fibroblast cell lines. For the first time, this study reports that DSE is a promising resource of anti-biofilm and anti-quorum sensing agents.

scholarly journals A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis

2021 ◽  
Vol 17 (9) ◽  
pp. e1009884 ◽  
Author(s):  
Junyan Liu ◽  
Hubertine M. E. Willems ◽  
Emily A. Sansevere ◽  
Stefanie Allert ◽  
Katherine S. Barker ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Vulvovaginal Candidiasis ◽  
Clinical Isolates ◽  
Vaginal Mucosa ◽  
Reading Frame ◽  
Human Fungal Pathogen ◽  
Vaginal Epithelial Cells ◽  
Life Issues

Vulvovaginal candidiasis (VVC), caused primarily by the human fungal pathogen Candida albicans, results in significant quality-of-life issues for women worldwide. Candidalysin, a toxin derived from a polypeptide (Ece1p) encoded by the ECE1 gene, plays a crucial role in driving immunopathology at the vaginal mucosa. This study aimed to determine if expression and/or processing of Ece1p differs across C. albicans isolates and whether this partly underlies differential pathogenicity observed clinically. Using a targeted sequencing approach, we determined that isolate 529L harbors a similarly expressed, yet distinct Ece1p isoform variant that encodes for a predicted functional candidalysin; this isoform was conserved amongst a collection of clinical isolates. Expression of the ECE1 open reading frame (ORF) from 529L in an SC5314-derived ece1Δ/Δ strain resulted in significantly reduced vaginopathogenicity as compared to an isogenic control expressing a wild-type (WT) ECE1 allele. However, in vitro challenge of vaginal epithelial cells with synthetic candidalysin demonstrated similar toxigenic activity amongst SC5314 and 529L isoforms. Creation of an isogenic panel of chimeric strains harboring swapped Ece1p peptides or HiBiT tags revealed reduced secretion with the ORF from 529L that was associated with reduced virulence. A genetic survey of 78 clinical isolates demonstrated a conserved pattern between Ece1p P2 and P3 sequences, suggesting that substrate specificity around Kex2p-mediated KR cleavage sites involved in protein processing may contribute to differential pathogenicity amongst clinical isolates. Therefore, we present a new mechanism for attenuation of C. albicans virulence at the ECE1 locus.

Antifungal susceptibilities, in vitro production of virulence factors and activities of ceragenins against Candida spp. isolated from vulvovaginal candidiasis

2018 ◽  
Vol 57 (3) ◽  
pp. 291-299 ◽  
Author(s):  
Mayram Hacioglu ◽  
Cagla Bozkurt Guzel ◽  
Paul B Savage ◽  
A Seher Birteksoz Tan
Keyword(s):  
Candida Albicans ◽  
Vulvovaginal Candidiasis ◽  
In Vitro Production ◽  
Candida Spp ◽  
Common Cause ◽  
Fluconazole Resistant ◽  
Resistant Strains ◽  
Vitro Production ◽  
Potential Use

Abstract Vulvovaginal candidiasis (VVC) is the second most common cause of vaginitis after bacterial vaginosis, affecting millions of women worldwide every year. Candida albicans is the most frequent agent of VVC followed by other species of Candida such as C. glabrata and C. parapsilosis. Out of a total of 100 clinical isolates of Candida spp. obtained from patients diagnosed with VVC, 84 were identified as C. albicans, while the remaining isolates were identified as non–-albicans Candida strains. Phospholipases and proteinases were produced by a majority of the C. albicans strains and esterases and hemolysins a minority of these strains. Among the non–C. albicans strains, only a few of the strains produced these proteins. Nearly all of the isolates formed biofilms. Our results showed that the butoconazole, clotrimazole, and fluconazole were active against C. albicans and less so against the non–albicans Candida strains. The MIC90 of amphotericin B and nystatins were 2 and 4 μg/ml, respectively, against either C. albicans or non–albicans Candida spp. Representative ceragenins (CSA-13, CSA-131, and CSA-138), developed as mimics of endogenous antimicrobial peptides, were active against fluconazole-resistant strains, both alone and in combination with fluconazole. These results suggest the potential use of ceragenins in treating VVC, including infections caused by fluconazole-resistant isolates.

scholarly journals A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis via altered secretion of candidalysin

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Junyan Liu ◽  
Emily Sansevere ◽  
Katherine Barker ◽  
Hubertine Willems ◽  
David Lowes ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amino Acid Sequences ◽  
Vulvovaginal Candidiasis ◽  
Clinical Isolates ◽  
Disease States ◽  
Peptide Toxin ◽  
Future Work

Background: Candida albicans is the primary etiological agent of vulvovaginal candidiasis (VVC) and exerts its pathogenicity through secretion of the peptide toxin candidalysin encoded by the ECE1 gene. A highly conserved variant ECE1 sequence exists across a diverse set of clinical isolates. Thus, we sought to determine the relative pathogenicity and mechanism(s) associated with this alternative ECE1 allele. Methods: Isogenic strains harboring WT or variant ECE1 sequences were engineered in an Δ/Δece1 background. After confirmation of equivalent expression by qPCR, pathogenicity of strains were tested using in vitro epithelial cell and in vivo VVC models of infection and LDH, IL-1β, neutrophil levels monitored. Follow up studies using synthetic candidalysin peptide were also performed. Lastly, a panel of ECE1 chimeras were constructed to assess potential processing defects and detected by a novel HiBiT-tagging approach. Results: Strains transformed with either the variant full length ECE1 or candidalysin allele, as compared to the WT sequence, demonstrated significantly reduced immunopathogenicity during in vitro or in vivo infection despite equivalent fungal burden. Interestingly, epithelial challenge with WT or variant synthetic peptide revealed similar capacity to elicit damage and IL-1β. Allele profiling and ECE1 chimera experiments demonstrated that defects in pathogenicity are at least partly due to inefficient ECE1 processing at the peptide 2-peptide 3 junction. Discussion: The ECE1 gene displays conserved polymorphisms that alter candidalysin secretion and strain pathogenicity. Future work is focused on determining specific amino acid sequences that contribute to these affects across clinical isolates and disease states.

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