scholarly journals Fungicidal Activity of Fluconazole against Candida albicans in a Synthetic Vagina-Simulative Medium

2004 ◽  
Vol 48 (1) ◽  
pp. 161-167 ◽  
Author(s):  
Mahomed-Yunus S. Moosa ◽  
Jack D. Sobel ◽  
Hussain Elhalis ◽  
Wenjin Du ◽  
Robert A. Akins
Keyword(s):  
Acetic Acid ◽  
Candida Albicans ◽  
Drug Development ◽  
Carboxylic Acids ◽  
Fungicidal Activity ◽  
Vaginal Candidiasis ◽  
Ph Range ◽  
Cure Rates ◽  
Systemic Infections

ABSTRACT Fluconazole (FLZ) has emerged as a highly successful agent in the management of systemic infections of Candida. Cure rates for symptomatic candidiasis following single 150-mg FLZ dose therapy exceed 90%. In vitro, however, FLZ is fungistatic only in a narrow pH range and is not effective at vaginal pH, 4.2. This study evaluated the effect of FLZ on Candida albicans under in vitro conditions resembling the vaginal microenvironment, using vagina-simulative medium (VS). We found that FLZ was fungicidal for C. albicans in VS, but not in other media at the same pH, 4.2. In VS, FLZ was fungicidal at concentrations of ≥8 μg/ml and reduced viability by greater than 99.9%. Analysis of the components of VS indicated that 17 mM acetic acid, a concentration achieved in the vagina, was responsible for the synergistic, fungicidal effect. This effect was not seen at neutral pH. Other substrates were not effective substitutes for acetic acid; however, short-chained carboxylic acids, glyoxylate and malonate, were effective. Most strains of C. albicans that were resistant to FLZ under standard conditions were killed by FLZ plus acetate. Other species of Candida were also killed, except C. krusei and C. glabrata. This study shows that FLZ has fungicidal activity for Candida species under in vitro conditions that mimic the vaginal microenvironment. This raises the possibility that FLZ may also have fungicidal effects during treatment of vaginal candidiasis. Elucidating the mechanism by which FLZ and acetate interact may disclose vulnerable pathways that could be exploited in drug development.

scholarly journals Some issues of the resistance of Candida glabrata to echinocandins

2019 ◽  
Vol 21 (4) ◽  
pp. 324-329
Author(s):  
Alexander V. Veselov
Keyword(s):  
Candida Albicans ◽  
Clinical Efficacy ◽  
Invasive Candidiasis ◽  
Candida Glabrata ◽  
Fungicidal Activity ◽  
Leading Position ◽  
Practical Guidelines ◽  
Systemic Infections ◽  
Selection Of

Invasive candidiasis is a common, severe and often difficult to treat complication in various categories of patients. Despite the fact that in most cases Candida albicans retains a leading position as an etiological cause, a pathogen such as Candida glabrata is becoming an increasingly relevant species, especially in oncohematology patients who have previously received therapy with azole antimycotics. For the treatment of systemic infections caused by C. glabrata, according to current versions of practical guidelines, echinocandins are the drugs of choice. Possessing high fungicidal activity, unlike azoles, they allow in most cases to achieve the clinical efficacy of therapy when this pathogen is isolated. However, there is an evidence of the selection of C. glabrata strains with reduced susceptibility or even resistance to echinocandins. This article briefly presents data on the problem of resistance of C. glabrata to drugs of this class, as well as the results of Russian in vitro studies.

Aktivitas Antifungi Air Perasan Bawang Merah (Allium ascalonicum L.) Terhadap Candida albicans Secara In Vitro

2017 ◽  
Vol 9 (2) ◽  
pp. 71
Author(s):  
Nurhasanah Nurhasanah ◽  
Fauzia Andrini ◽  
Yulis Hamidy
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Allium Sativum ◽  
Fungicidal Activity ◽  
Positive Control ◽  
Negative Control ◽  
Randomized Design ◽  
Significant Difference ◽  
Completely Randomized Design

Shallot (Allium ascalonicum L.) has been known as traditional medicine. Shallot which has same genus with garlic(Allium sativum L.) contains allicin that is also found in garlic and has been suspected has fungicidal activity toCandida albicans. It is supported by several researches. Therefore, shallot is suspected has antifungal activity too.The aim of this research was to know antifungal activity of shallot’s water extortion againsts Candida albicans invitro. This was a laboratory experimental research which used completely randomized design, with diffusion method.Shallot’s water extortion was devided into three concentrations, there were 50%, 100% and 200%. Ketoconazole 2%was positive control and aquadest was negative control. The result of this research based on analysis of varians(Anova), there was significant difference between several treatments and was confirmed with Duncan New MultipleRange Test (DNMRT) p<0,05, there was significant difference between 100% shallot’s water extortion with othertreatments, but there was no significant difference between 50% shallot’s water extortion with 200% shallot’s. Theconclusion was shallot’s water extortion had antifungal activity againsts Candida albicans with the best concentration100%, but it was lower than ketoconazole 2%.

Interaction of Candida albicans with genital mucosa: effect of sex hormones on adherence of yeasts in vitro

1988 ◽  
Vol 34 (3) ◽  
pp. 224-228 ◽  
Author(s):  
Aliza Kalo ◽  
Esther Segal
Keyword(s):  
Candida Albicans ◽  
Hela Cell ◽  
Sex Hormones ◽  
Hela Cells ◽  
Cell Types ◽  
Vaginal Candidiasis ◽  
Genital Mucosa ◽  
Hela Cell Lines ◽  
I Cells

Findings from our previous studies revealed a correlation between the level of adherence in vitro of Candida albicans to human exfoliated vaginal epithelial cells (VEC) and the hormonal status of the cell donors. In the present study we investigated the effect of the sex hormones estradiol, estriol, progesterone, and testosterone on the binding of the yeasts to HeLa cell lines and VEC in vitro. Monolayers of HeLa cells were exposed to the hormones and yeasts under controlled conditions. The number of adherent yeasts per square millimetre of HeLa cell monolayers and the percentage of VEC with adherent yeasts was estimated by microscopic counts. The results showed that the tested sex hormones affected at various degrees the adhesion of yeasts to HeLa cells or VEC. Progesterone had the most marked effect, leading to a significant increase in the number of adherent yeasts to HeLa cells or in the percentage of adhesion of VEC. In addition, VEC were separated on Percoll gradients into the two cell types: superficial (S) and intermediate (I), cell types which appear physiologically under increased serum levels of estradiol or progesterone, respectively. Adhesion assays with the separated cell populations revealed an increased binding capacity of the I cells. The finding that progesterone increased the adherence of yeasts to genital mucosa and that VEC of the I type have a higher capacity to adhere the yeasts is compatible with our previous observation that increased numbers of I cells, appearing under high level of progesterone, are found in situations known to have predisposition to vaginal candidiasis. Thus, our data point to a possible involvement of the hormone progesterone in the adherence of C. albicans to genital epithelium.

scholarly journals Effect of β-1,6-Glucan Inhibitors on the Invasion Process of Candida albicans: Potential Mechanism of Their In Vivo Efficacy

2009 ◽  
Vol 53 (9) ◽  
pp. 3963-3971 ◽  
Author(s):  
Akihiro Kitamura ◽  
Saito Higuchi ◽  
Masato Hata ◽  
Katsuhiro Kawakami ◽  
Kumi Yoshida ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Critical Role ◽  
Vaginal Candidiasis ◽  
Specific Cell ◽  
Cell Wall Proteins ◽  
Invasion Process ◽  
In Vivo Efficacy

ABSTRACT β-1,6-Glucan is a fungus-specific cell wall component that is essential for the retention of many cell wall proteins. We recently reported the discovery of a small molecule inhibitor of β-1,6-glucan biosynthesis in yeasts. In the course of our study of its derivatives, we found a unique feature in their antifungal profile. D21-6076, one of these compounds, exhibited potent in vitro and in vivo antifungal activities against Candida glabrata. Interestingly, although it only weakly reduced the growth of Candida albicans in conventional media, it significantly prolonged the survival of mice infected by the pathogen. Biochemical evaluation of D21-6076 indicated that it inhibited β-1,6-glucan synthesis of C. albicans, leading the cell wall proteins, which play a critical role in its virulence, to be released from the cell. Correspondingly, adhesion of C. albicans cells to mammalian cells and their hyphal elongation were strongly reduced by the drug treatment. The results of the experiment using an in vitro model of vaginal candidiasis showed that D21-6076 strongly inhibited the invasion process of C. albicans without a significant reduction in its growth in the medium. These evidences suggested that D21-6076 probably exhibited in vivo efficacy against C. albicans by inhibiting its invasion process.

scholarly journals Gene Overexpression/Suppression Analysis of Candidate Virulence Factors of Candida albicans

2008 ◽  
Vol 7 (3) ◽  
pp. 483-492 ◽  
Author(s):  
Yue Fu ◽  
Guanpingsheng Luo ◽  
Brad J. Spellberg ◽  
John E. Edwards ◽  
Ashraf S. Ibrahim
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Surface Proteins ◽  
Screening Tests ◽  
Vaginal Candidiasis ◽  
Loss Of Function ◽  
Genes Encoding ◽  
Gpi Proteins ◽  
Protein Cell

ABSTRACT We developed a conditional overexpression/suppression genetic strategy in Candida albicans to enable simultaneous testing of gain or loss of function in order to identify new virulence factors. The strategy involved insertion of a strong, tetracycline-regulated promoter in front of the gene of interest. To validate the strategy, a library of genes encoding glycosylphosphatidylinositol (GPI)-anchored surface proteins was screened for virulence phenotypes in vitro. During the screening, overexpression of IFF4 was found to increase the adherence of C. albicans to plastic and to human epithelial cells, but not endothelial cells. Consistent with the in vitro results, IFF4 overexpression modestly increased the tissue fungal burden during murine vaginal candidiasis. In addition to the in vitro screening tests, IFF4 overexpression was found to increase C. albicans susceptibility to neutrophil-mediated killing. Furthermore, IFF4 overexpression decreased the severity of hematogenously disseminated candidiasis in normal mice, but not in neutropenic mice, again consistent with the in vitro phenotype. Overexpression of 12 other GPI proteins did not affect normal GPI protein cell surface accumulation, demonstrating that the overexpression strategy did not affect the cell capacity for making such proteins. These data indicate that the same gene can increase or decrease candidal virulence in distinct models of infection, emphasizing the importance of studying virulence genes in different anatomical contexts. Finally, these data validate the use of a conditional overexpression/suppression genetic strategy to identify candidal virulence factors.

scholarly journals Fungicidal activity of rabbit alveolar and peritoneal macrophages against Candida albicans

1980 ◽  
Vol 28 (3) ◽  
pp. 1001-1008
Author(s):  
R I Lehrer ◽  
L G Ferrari ◽  
J Patterson-Delafield ◽  
T Sorrell
Keyword(s):  
Candida Albicans ◽  
Alveolar Macrophages ◽  
Fungicidal Activity ◽  
Peritoneal Macrophages ◽  
Human Monocytes ◽  
Blood Monocytes ◽  
Human Granulocytes ◽  
The Mean ◽  
Macrophage Populations

We tested the ability of rabbit macrophages to kill Candida albicans in vitro. Resident (unstimulated) alveolar macrophages killed 28.1 +/- 1.9% of ingested organisms in 4 h, whereas resident peritoneal macrophages killed only 15.2 +/- 1.3% (mean +/- standard error of the mean, P < 0.01). Peritoneal macrophages obtained from rabbits treated 3 weeks earlier with complete Freund adjuvant showed enhanced candidacidal activity relative to normally resident peritoneal cells (28.2 +/- 3.1%, P < 0.01). Candidacidal activity by alveolar macrophages recovered from such treated animals was slightly enhanced relative to untreated alveolar macrophages (32.9 +/- 2.3%). Candidacidal activity by peritoneal and alveolar macrophages was not decreased by several agents (cyanide, azide, sulfadiazine, and phenylbutazone) that inhibit the ability of human blood monocytes to kill C. albicans. In contrast, candidacidal activity by alveolar macrophages was greatly diminished by iodoacetate, an ineffective inhibitor of this function in human monocytes. We conclude that rabbit macrophages kill C. albicans by a fungicidal mechanism distinct from the peroxidase-H2O2 mechanism of human granulocytes and monocytes, and that the fungicidal properties of peritoneal and alveolar macrophage populations are enhanced after nonspecific stimulation with complete Freund adjuvant.

scholarly journals In Vitro Activity of a New Polyene, SPA-S-843, against Yeasts

1998 ◽  
Vol 42 (11) ◽  
pp. 3012-3013 ◽  
Author(s):  
C. Rimaroli ◽  
T. Bruzzese
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Tropicalis ◽  
Candida Glabrata ◽  
Fungicidal Activity ◽  
Candida Krusei ◽  
Water Soluble ◽  
Vitro Activity ◽  
In Vitro Activity

ABSTRACT The in vitro activity of a new water-soluble polyene, SPA-S-843, was evaluated against 116 strains of Candida,Cryptococcus, and Saccharomyces spp. and compared with that of amphotericin B. SPA-S-843 demonstrated better inhibitory activity against all of the yeasts examined and better fungicidal activity against Candida albicans, Candida glabrata, Candida krusei, and Candida tropicalis than did amphotericin B.

In Vitro Antifungal Activity of Clove Oil against Candida Albicans Isolated from Clinical Samples

2018 ◽  
Vol 11 (2) ◽  
pp. 4021-4025
Author(s):  
Noura Berakdar ◽  
Abdulkarim Radwan
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
In Vitro Study ◽  
Inhibition Zone ◽  
University Hospital ◽  
Vaginal Candidiasis ◽  
Clinical Samples ◽  
Clove Oil ◽  
Antifungal Antibiotics

The main goal of this study was to investigate the antifungal activity of clove oil against candida albicans of vaginal candidiasis in females from Syria. An in vitro study was carried out using the following Candida albicans strains involved in vaginal candidiasis using the well diffusion (WD) testing.Candida albicans (ATCC 90028) and 15 strains were compiled from Aleppo University Hospital. These strains were collected from women having vaginal candidiasis. The antifungal activity of clove oil was determined in the form of inhibition zone using antifungal assay by agar WD testing.In all experiments, the obtained results indicated that clove oil has inhibitory effects on Candida albicans (ATCC 90028) and against15 fungal strains. This study showed that clove oil was active against the tested Candida albicans strains. Clove oil was more effective against Candida albicans compared to the antifungal antibiotics nystatin, ketoconazole and itraconazol. Clove oil may have potential for use in the development of clinically useful antifungal preparations. Therefore, clove oil might be clinically effective in the natural prevention treatment of vaginal candidiasis.       

LL37 and hBD-3 elevate the β-1,3-exoglucanase activity of Candida albicans Xog1p, resulting in reduced fungal adhesion to plastic

2012 ◽  
Vol 441 (3) ◽  
pp. 963-970 ◽  
Author(s):  
Hao-Teng Chang ◽  
Pei-Wen Tsai ◽  
Hsin-Hui Huang ◽  
Yu-Shu Liu ◽  
Tzu-Shan Chien ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antimicrobial Peptides ◽  
Organ Transplant ◽  
Vaginal Candidiasis ◽  
Immunocompromised Patients ◽  
Fungal Adhesion ◽  
Oral Thrush ◽  
Dose Dependent

The opportunistic fungus Candida albicans causes oral thrush and vaginal candidiasis, as well as candidaemia in immunocompromised patients including those undergoing cancer chemotherapy, organ transplant and those with AIDS. We previously found that the AMPs (antimicrobial peptides) LL37 and hBD-3 (human β-defensin-3) inhibited C. albicans viability and its adhesion to plastic. For the present study, the mechanism by which LL37 and hBD-3 reduced C. albicans adhesion was investigated. After AMP treatment, C. albicans adhesion to plastic was reduced by up to ~60% and was dose-dependent. Our previous study indicated that LL37 might interact with the cell-wall β-1,3-exoglucanase Xog1p, which is involved in cell-wall β-glucan metabolism, and consequently the binding of LL37 or hBD-3 to Xog1p might cause the decrease in adhesion. For the present study, Xog1p(41–438)-6H, an N-terminally truncated, active, recombinant construct of Xog1p and Xog1p fragments were produced and used in pull-down assays and ELISA in vitro, which demonstrated that all constructs interacted with both AMPs. Enzymatic analyses showed that LL37 and hBD-3 enhanced the β-1,3-exoglucanase activity of Xog1p(41–438)-6H approximately 2-fold. Therefore elevated Xog1p activity might compromise cell-wall integrity and decrease C. albicans adhesion. To test this hypothesis, C. albicans was treated with 1.3 μM Xog1p(41–438)-6H and C. albicans adhesion to plastic decreased 47.7%. Taken together, the evidence suggests that Xog1p is one of the LL37/hBD-3 targets, and elevated β-1,3-exoglucanase activity reduces C. albicans adhesion to plastic.

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