scholarly journals Fungicidal Activity of a Safe 1,3,4-Oxadiazole Derivative Against Candida albicans

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 314
Author(s):  
Daniella Renata Faria ◽  
Raquel Cabral Melo ◽  
Glaucia Sayuri Arita ◽  
Karina Mayumi Sakita ◽  
Franciele Abigail Vilugron Rodrigues-Vendramini ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungicidal Activity ◽  
Inhibitory Concentration ◽  
Therapeutic Potential ◽  
Bloodstream Infections ◽  
Common Species ◽  
Future Application ◽  
Chemical Similarity ◽  
Preclinical Trials

Candida albicans is the most common species isolated from nosocomial bloodstream infections. Due to limited therapeutic arsenal and increase of drug resistance, there is an urgent need for new antifungals. Therefore, the antifungal activity against C. albicans and in vivo toxicity of a 1,3,4-oxadiazole compound (LMM6) was evaluated. This compound was selected by in silico approach based on chemical similarity. LMM6 was highly effective against several clinical C. albicans isolates, with minimum inhibitory concentration values ranging from 8 to 32 µg/mL. This compound also showed synergic effect with amphotericin B and caspofungin. In addition, quantitative assay showed that LMM6 exhibited a fungicidal profile and a promising anti-biofilm activity, pointing to its therapeutic potential. The evaluation of acute toxicity indicated that LMM6 is safe for preclinical trials. No mortality and no alterations in the investigated parameters were observed. In addition, no substantial alteration was found in Hippocratic screening, biochemical or hematological analyzes. LMM6 (5 mg/kg twice a day) was able to reduce both spleen and kidneys fungal burden and further, promoted the suppresses of inflammatory cytokines, resulting in infection control. These preclinical findings support future application of LMM6 as potential antifungal in the treatment of invasive candidiasis.

Comparison of antifungal efficacies of moxifloxacin, liposomal amphotericin B, and combination treatment in experimental Candida albicans endophthalmitis in rabbits

2010 ◽  
Vol 56 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Yudum Tiftikcioğlu Deren ◽  
Şengül Özdek ◽  
Ayşe Kalkanci ◽  
Nalan Akyürek ◽  
Berati Hasanreisoğlu
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Amphotericin B ◽  
Combination Treatment ◽  
Liposomal Amphotericin ◽  
Inhibitory Concentration ◽  
Liposomal Amphotericin B ◽  
Control Group

The goal of this study was to compare in vitro and in vivo efficacy of moxifloxacin and liposomal amphotericin B (Amp-B) monotherapies and combination treatment against Candida albicans in an exogenous endophthalmitis model in rabbit eyes. Microplate dilution tests and checkerboard analysis were performed to detect in vitro efficacies. Endophthalmitis was induced by intravitreal injection of C. albicans in 40 rabbit eyes with simultaneous intravitreal drug injection according to prophylactic treatment groups. Group 1 (control group) received 0.1 mL of balanced salt solution, group 2 (moxi group) 100 µg moxifloxacin/0.1 mL, group 3 (Amp-B group) 10 µg liposomal Amp-B/0.1 mL, and group 4 (combi group) both 100 µg moxifloxacin/0.05 mL and 10 µg liposomal Amp-B/0.05 mL intravitreally. Clinical examination, quantitative analysis of microorganisms, and histopathologic examination were performed as in vivo studies. The minimum inhibitory concentration of liposomal Amp-B against C. albicans was found to be 1 µg/mL. Moxifloxacin showed no inhibition of in vitro C. albicans growth. The minimum inhibitory concentration values of liposomal Amp-B for C. albicans were reduced two- to eightfold with increasing concentrations of moxifloxacin in vitro. In vivo, there was no C. albicans growth in the combi group (zero of eight eyes), whereas three eyes (37.5%) showed growth in the Amp-B group. Vitreous inflammation, retinal detachment, focal retinal necrosis, and outer nuclear layer loss were found to be lower in the moxi group compared with the control group. Ganglion cell and inner nuclear layer loss was observed in all eyes (100%) in both the moxi and combi groups, whereas only in 25% (two of eight eyes) in the Amp-B group. Moxifloxacin strongly augments the efficacy of liposomal Amp-B against C. albicans in vitro, although it has no in vitro antifungal activity when used alone. It is interesting that we found a synergistic effect for in vitro tests but failed to demonstrate it in vivo. When 100 µg moxifloxacin/0.1 mL is given intravitreally, it has some toxic effects that are limited to the inner retinal layers.

scholarly journals Minimal Inhibitory Concentration (MIC)-Phenomena in Candida albicans and Their Impact on the Diagnosis of Antifungal Resistance

2019 ◽  
Vol 5 (3) ◽  
pp. 83 ◽  
Author(s):  
Ulrike Binder ◽  
Maria Aigner ◽  
Brigitte Risslegger ◽  
Caroline Hörtnagl ◽  
Cornelia Lass-Flörl ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Treatment Response ◽  
Minimal Inhibitory Concentration ◽  
Antifungal Therapy ◽  
Inhibitory Concentration ◽  
Galleria Mellonella ◽  
Antifungal Susceptibility ◽  
Infection Model ◽  
The Impact

Antifungal susceptibility testing (AFST) of clinical isolates is a tool in routine diagnostics to facilitate decision making on optimal antifungal therapy. The minimal inhibitory concentration (MIC)-phenomena (trailing and paradoxical effects (PXE)) observed in AFST complicate the unambiguous and reproducible determination of MICs and the impact of these phenomena on in vivo outcome are not fully understood. We aimed to link the MIC-phenomena with in vivo treatment response using the alternative infection model Galleria mellonella. We found that Candida albicans strains exhibiting PXE for caspofungin (CAS) had variable treatment outcomes in the Galleria model. In contrast, C. albicans strains showing trailing for voriconazole failed to respond in vivo. Caspofungin- and voriconazole-susceptible C. albicans strains responded to the respective antifungal therapy in vivo. In conclusion, MIC data and subsequent susceptibility interpretation of strains exhibiting PXE and/or trailing should be carried out with caution, as both effects are linked to drug adaptation and treatment response is uncertain to predict.

scholarly journals Effects of Echinocandins in Combination with Nikkomycin Z against Invasive Candida albicans Bloodstream Isolates and the fks Mutants

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Yuk-Yam Cheung ◽  
Mamie Hui
Keyword(s):  
Candida Albicans ◽  
Therapeutic Potential ◽  
Synergistic Effects ◽  
Rank Test ◽  
Content Type ◽  
Log Rank Test ◽  
Echinocandin Resistance ◽  
Nikkomycin Z

ABSTRACT We evaluated the in vitro and in vivo effects of nikkomycin Z combined with an echinocandin (anidulafungin or micafungin) against two Candida albicans isolates and their lab-derived echinocandin-resistant fks mutants with FKS1 S645Y and FKS1 S645P. Synergistic effects were observed in all tested strains (fractional inhibitory concentration index, <0.5). Enhanced survival was observed in an immunocompromised murine model (log-rank test, P < 0.02). Our study demonstrated the therapeutic potential of nikkomycin Z-echinocandin combinations in managing echinocandin resistance.

scholarly journals Lovastatin Has Significant Activity against Zygomycetes and Interacts Synergistically with Voriconazole

2006 ◽  
Vol 50 (1) ◽  
pp. 96-103 ◽  
Author(s):  
Georgios Chamilos ◽  
Russell E. Lewis ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Fungicidal Activity ◽  
Inhibitory Concentration ◽  
Effective Concentration ◽  
Significant Activity ◽  
In Vitro Activity ◽  
Testing Methods ◽  
Disk Diffusion Testing ◽  
Dye Staining

ABSTRACT Zygomycetes are emerging opportunistic molds resistant to most conventional antifungals. We evaluated the in vitro activity of lovastatin (LOV), a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, against seven clinical isolates of Zygomycetes by using standard microdilution methods in three different media, disk diffusion testing, and viability dye staining. To further study the in vivo efficacy of LOV against zygomycetes, we developed a Drosophila melanogaster model of zygomycosis. In different experiments, groups of Toll-deficient (Tl) flies fed LOV-containing food were subsequently injected with two representative Zygomycetes isolates (Mucor and Rhizopus spp.). Finally, we examined the effects of LOV on voriconazole (VRC) activity against zygomycetes in vitro by checkerboard dilution, Epsilometer test-based methods, and bis-(1,3-dibutylbarbituric acid) trimethine oxonol staining and in vivo in Tl flies fed food containing LOV plus VRC and infected with zygomycetes. LOV exhibited significant, medium, and strain-independent fungicidal activity against all Zygomycetes isolates in vitro by all testing methods (MIC50, 48.0 μg/ml; 50% minimal fungicidal concentration, 56.0 μg/ml; 50% effective concentration, 29.4 μg/ml [6.6 to 38.9 μg/ml]). Tl flies fed LOV-containing food and infected with Mucor had a significantly better 6-day survival rate than did infected Tl flies fed regular food (P = 0.0005). LOV displayed in vitro synergy with VRC against all Zygomycetes isolates (fractional inhibitory concentration index, 0.104 to 0.290) by all methods used. LOV also displayed synergy with VRC in the Drosophila model of zygomycosis (P < 0.01). LOV is significantly active against zygomycetes and synergizes with triazoles inherently resistant to them, such as VRC. The clinical significance of these findings needs to be further explored.

scholarly journals Cytosporone B as a Biological Preservative: Purification, Fungicidal Activity and Mechanism of Action against Geotrichum citri-aurantii

Biomolecules ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 125 ◽  
Author(s):  
Chunxiao Yin ◽  
Hongxin Liu ◽  
Yang Shan ◽  
Vijai Gupta ◽  
Yueming Jiang ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Cell Membrane ◽  
Fungicidal Activity ◽  
Inhibitory Concentration ◽  
Membrane Integrity ◽  
Action Mechanism ◽  
Fungal Cell ◽  
Effect Concentration ◽  
Biological Preservative

To prevent citrus decay caused by Geotrichum citri-aurantii, 12 natural products were isolated from two endophytic fungi, in which cytosporone B was shown to have excellent bioactivity for control of G. citri-aurantii with median effect concentration (EC50) of 26.11 μg/mL and minimum inhibitory concentration (MIC) of 105 μg/mL, and also significantly reduced the decay of sugar orange during the in vivo trials. In addition, cytosporone B could alter the morphology of G. citri-aurantii by causing distortion of the mycelia and loss of membrane integrity. Differentially expressed genes (DEGs) between cytosporone B-treated and -untreated samples were revealed by Illumina sequencing, including 3540 unigenes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that most DEGs were related to metabolic production and cell membrane. These findings suggest cytosporone B is a promising biological preservative to control citrus decay and reveal the action mechanism of cytosporone B in relation to the destruction of the fungal cell membrane at both morphological and molecular levels.

scholarly journals Susceptibility To Caspofungin And Fluconazole And Als1/Als3 Gene Expression In Biofilm And Dispersal Cells Of Candida Albicans / Profil Osjetljivosti Na Kaspofungin I Flukonazol I Ekspresija Gena Als1 I Als3 U Stanicama Biofilma Te Planktonskim Stanicama Vrste Candida Albicans

2012 ◽  
Vol 63 (4) ◽  
pp. 497-503 ◽  
Author(s):  
Helena Bujdáková ◽  
Naďa Kulková ◽  
Lucia Černáková
Keyword(s):  
Candida Albicans ◽  
Liquid Culture ◽  
Inhibitory Concentration ◽  
Bloodstream Infections ◽  
High Expression ◽  
Risk Of Infection ◽  
Quantitative Real Time Pcr ◽  
Planktonic Cells ◽  
Reduction Assay ◽  
Time Of Administration

AbstractThe biofilm of Candida albicans has been implicated as a source of bloodstream infections. Dispersal cells, as the final biofilm stage, are responsible for its spread. The aim of this study was to compare the susceptibility of biofilm and dispersal cells vs. planktonic cells (overnight liquid culture) of C. albicans to caspofungin (CAS) and fluconazole (FLU) when the drugs were added: i) at the beginning of the experiment; ii) after 1.5 h (adherence stage); iii) after 24 h (early mature biofilm). The findings were evaluated after 48 h (mature biofilm) using the XTT reduction assay. Later administration of the drug increased biofilm sessile minimal inhibitory concentration (SMIC80) of both FLU and CAS from 1 μg mL-1 to over 64 μg mL-1 and from 0.125 μg mL-1 to over 16 μg mL-1, respectively. Susceptibility of dispersal cells also decreased with time of administration.We also determined the expression of the Als1 and Als3 genes in 48-h sessile biofilm and dispersal cells of C. albicans SC5314 and compared it to planktonic cells. The expression was normalised to the standard Act1 gene in every condition tested. Quantitative real-time PCR revealed a strong up-regulation of the Als1 gene in the dispersal cells but not in biofilm and high expression of the Als3 gene in both biofilm and dispersal cells. High expression of both Als1 and Als3 genes supports the hypothesis that dispersal cells pose a high-risk of infection.

scholarly journals Effect of hydroalcoholic leaves extract of Datura stramonium on pathogenic Candida albicans

2015 ◽  
Vol 39 (2) ◽  
pp. 55-61
Author(s):  
Ali Y. Salman
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Datura Stramonium ◽  
In Vitro Test ◽  
In Vivo Test ◽  
Vitro Test

      This research aimed at studying the effect of different concentration of hydroalcoholic leaves extract of Datura stramonium concentration against pathogenic Candida albicans isolated from clinical cases of diarrhea in cows and dogs in Baghdad province. Hydroalcoholic extract of the leaves of Datura stramonium were prepared in different concentrations for In vitro and In vivo study against Candida albicans. In vitro test includes the determination of minimum inhibitory concentration 50, 25, 12.5, 6.25, 3.12 and 1.75mg/1ml), and it was found that the minimum inhibitory concentration was 3.12 mg/1ml. Whereas the in vivo test was performed for the determination of sensitivity test of Candida albicans in concentration of plant 10, 15 and 20 mg/1ml which was compared with same concentration of Nystatin. The study was performed in seven groups of mice according to different concentrations. The infective dose of Candida albicans was 1X108, which was proved by histopathology changes after eight day. The result obtained from invivo study revealed that after the end of the therapeutic period that lasted for 8 days. Confirm the efficacy of Datura stramonium extract at 20% as a treatment for mice infected with Candida albicans.

scholarly journals Antibiotic Activity of a Paraphaeosphaeria sporulosa-Produced Diketopiperazine against Salmonella enterica

2020 ◽  
Vol 6 (2) ◽  
pp. 83
Author(s):  
Raffaele Carrieri ◽  
Giorgia Borriello ◽  
Giulio Piccirillo ◽  
Ernesto Lahoz ◽  
Roberto Sorrentino ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Salmonella Enterica ◽  
Inhibitory Concentration ◽  
Animal Husbandry ◽  
Antibiotic Activity ◽  
Future Application ◽  
Liquid Chromatography Mass Spectrometry ◽  
In Vivo Experiments ◽  
First Time

A diketopiperazine has been purified from a culture filtrate of the endophytic fungus Paraphaeosphaeria sporulosa, isolated from healthy tissues of strawberry plants in a survey of microbes as sources of anti-bacterial metabolites. Its structure has been determined by nuclear magnetic resonance (NMR) and liquid chromatography–mass spectrometry (LC–MS) analyses and was found to be identical to cyclo(L-Pro-L-Phe) purified from species of other fungal genera. This secondary metabolite has been selected following bioguided-assay fractionation against two strains of Salmonella enterica, the causal agent of bovine gastroenteritis. The diketopiperazine cyclo(L-Pro-L-Phe), isolated for the first time from Paraphaeosphaeria species, showed minimum inhibitory concentration (MIC) values of 71.3 and 78.6 μg/mL against the two S. enterica strains. This finding may be significant in limiting the use of synthetic antibiotics in animal husbandry and reducing the emergence of bacterial multidrug resistance. Further in vivo experiments of P. sporulosa diketopiperazines are important for the future application of these metabolites.

scholarly journals In Vitro Profiling of Pramiconazole and In Vivo Evaluation in Microsporum canis Dermatitis and Candida albicans Vaginitis Laboratory Models

2010 ◽  
Vol 54 (11) ◽  
pp. 4927-4929 ◽  
Author(s):  
Kelly de Wit ◽  
Caroline Paulussen ◽  
An Matheeussen ◽  
Koen van Rossem ◽  
Paul Cos ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Guinea Pig ◽  
Inhibitory Concentration ◽  
Topical Administration ◽  
Microsporum Canis ◽  
In Vivo Evaluation ◽  
Guinea Pig Model ◽  
Laboratory Models

ABSTRACT The triazole antifungal pramiconazole (Stiefel, a GSK company) was compared with itraconazole, miconazole, and terbinafine in vitro and in vivo. Potent in vitro activities against Candida spp. (50% inhibitory concentration [IC50], 0.04 to 1.83 μM) and Microsporum and Trichophyton spp. (IC50, 0.15 to 1.34 μM) were obtained but not, however, against other filamentous molds and zygomycetes. In the M. canis guinea pig model and C. albicans vulvovaginitis rat model, pramiconazole was superior to the reference compounds after oral and topical administration.

scholarly journals Enhanced Killing of Candida albicans by Human Macrophages Adherent to Type 1 Collagen Matrices via Induction of Phagolysosomal Fusion

2005 ◽  
Vol 73 (2) ◽  
pp. 770-777 ◽  
Author(s):  
Simon L. Newman ◽  
Bindu Bhugra ◽  
Angela Holly ◽  
Randal E. Morris
Keyword(s):  
Candida Albicans ◽  
Alimentary Tract ◽  
Fungicidal Activity ◽  
Invasive Fungal Disease ◽  
Matrix Proteins ◽  
Human Macrophage ◽  
Collagen Matrices ◽  
Monocytes And Macrophages

ABSTRACT Candida albicans, a component of the normal flora of the alimentary tract and mucocutaneous membranes, is the leading cause of invasive fungal disease in premature infants, diabetics, and surgical patients and of oropharyngeal disease in AIDS patients. As little is known about the regulation of monocyte/macrophage anti-Candida activity, we sought to determine if fungicidal activity might be regulated by extracellular matrix proteins to which monocytes/macrophages are adherent in vivo. Compared to monocyte/macrophages that adhered to plastic, human monocytes and monocyte-derived macrophages that adhered to type 1 collagen matrices, but not to fibronectin, vitronectin, or laminin, demonstrated a significant increase in candidacidal activity. The enhancement of monocyte fungicidal activity was maintained over a 4-h period, whereas macrophage fungicidal activity was maximum at 1 h. Although adherence of monocytes and macrophages to collagen matrices concomitantly enhanced the production of superoxide anion, only the fungicidal activity of collagen-adherent monocytes was partially blocked by superoxide dismutase and catalase. Remarkably, we found that only 10% of the phagosomes in C. albicans-infected macrophages that adhered to plastic fused with lysosomes. In contrast, 80% of yeast-containing phagosomes of collagen-adherent macrophages fused with lysosomes. These data suggest that nonoxidative mechanisms are critical for human macrophage anti-Candida activity and that C. albicans pathogenicity is mediated, in part, by its ability to inhibit phagolysosomal fusion in macrophages.

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