Effet cytotoxique in vitro et chez l'insecte hôte des destruxines, toxines cyclodepsipeptidiques produites par le champignon entomopathogène Metarhizium anisopliae

1989 ◽  
Vol 35 (11) ◽  
pp. 1000-1008 ◽  
Author(s):  
A. Vey ◽  
J. M. Quiot
Keyword(s):  
Cytotoxic Effect ◽  
Galleria Mellonella ◽  
Fungal Infections ◽  
Ultrastructural Level ◽  
Malpighian Tubules ◽  
In Vitro Toxicity ◽  
Cytotoxic Action ◽  
Champignon Entomopathogène ◽  
Molecular Aspects

The cytotoxic effect of the cyclodepsipeptide mycotoxins of the group of destruxins (DA, DB, DE) has been investigated in the insect host, Galleria mellonella, and in invertebrate cell cultures, mainly at the ultrastructural level. The strong effect of DE is characterized by changes in the morphology of the cells, and the development of structural alterations at the nuclear and cytoplasmic levels. The major lesions observed even at low doses consist in a pycnotic evolution of the nucleus and a degradation of mitochondria, while the rough endoplasmic reticulum and the ribosomes are also impaired. In the host, the main organs and tissues attacked by DE are the midgut, the malpighian tubules, and the circulating hemocytes. A comparative study of the effect of DE, DA, and DB has revealed a specificity in the cytotoxic action of these compounds. The following classification has been observed in the efficiency of the molecules: DE > DA > DB. These results allow a better understanding of the role of peptidic mycotoxins in the pathogenesis of fungal infections. They also reveal similarities with the action of other mycotoxins, and constitute a valuable foundation for studies on the molecular aspects of the mechanism of action of destruxins.Key words: mycotoxin, destruxin, mode of action, cytotoxic effect, in vitro toxicity.

scholarly journals Efficacy of Antifungal Monotherapies and Combinations againstAspergillus calidoustus

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
E. Glampedakis ◽  
A. T. Coste ◽  
M. Aruanno ◽  
D. Bachmann ◽  
E. Delarze ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Therapeutic Range ◽  
Potential Benefit ◽  
Galleria Mellonella ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Content Type ◽  
Content Model ◽  
Poor Outcomes

ABSTRACTInvasive fungal infections due toAspergillus calidoustuswith decreased azole susceptibility are emerging in the setting of azole prophylaxis and are associated with poor outcomes. We assessed thein vitroactivity of antifungal drugs used alone or in combinations againstA. calidoustusand found a synergistic effect between voriconazole and terbinafine at concentrations within the therapeutic range. An invertebrateGalleria mellonellamodel ofA. calidoustusinfection tended to support the potential benefit of this combination.

In Vitro Toxicity to Two Cellular Systems of the First Ten Chemicals on the MEIC List

1990 ◽  
Vol 17 (3) ◽  
pp. 218-223
Author(s):  
Xavier Ponsoda ◽  
Ramiro Jover ◽  
José Vicente Castell ◽  
Mariá José Gómez-Lechón
Keyword(s):  
Acetylsalicylic Acid ◽  
Ferrous Sulphate ◽  
Rat Hepatocytes ◽  
Cellular Protein ◽  
Cellular Systems ◽  
In Vitro Toxicity ◽  
Cytotoxic Action ◽  
Hepatic Cells ◽  
Cellular Protein Content

The cytotoxic effects of the first 10 chemicals on the MEIC list were evaluated with two experimental cellular systems, monolayer cultures of rat hepatocytes and cell lines (Hep G2 and 3T3). Three endpoints were measured to evaluate cytotoxicity, intracellular LDH activity, cellular protein content and the MTT test. The results show that: 1. digoxin, amitriptyline and diazepam were the most cytotoxic chemicals (IC50:0.01-0.5mM); 2. alcoholic compounds (sopropanol, ethylene glycol, ethanol and methanol) produced the lowest toxic effects (IC50: 100–1500mM); 3. paracetamol, acetylsalicylic acid and ferrous sulphate showed an intermediate cytotoxic action (C50: 0.05–15mM); 4. regarding the sensitivity of the cellular systems, paracetamol, acetylsalicylic acid, diazepam and ferrous sulphate were more toxic to rat hepatocytes, while digoxin produced a different toxic effect on hepatic and non-hepatic cells; and 5. the other chemicals did not show significant differences in their toxicity in the different cellular systems studied.

scholarly journals In Vitro or in Vivo Models, the Next Frontier for Unraveling Interactions between Malassezia spp. and Hosts. How Much do We Know?

2020 ◽  
Author(s):  
Maritza Torres ◽  
Hans De Cock ◽  
Adriana Marcela Celis Ramírez
Keyword(s):  
Galleria Mellonella ◽  
Fungal Infections ◽  
Ex Vivo ◽  
Model Organisms ◽  
In Vivo Models ◽  
Fungal Host ◽  
Alternative Models ◽  
Malassezia Spp

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

scholarly journals In Vitro or In Vivo Models, the Next Frontier for Unraveling Interactions between Malassezia spp. and Hosts. How Much Do We Know?

2020 ◽  
Vol 6 (3) ◽  
pp. 155
Author(s):  
Maritza Torres ◽  
Hans de Cock ◽  
Adriana Marcela Celis Ramírez
Keyword(s):  
Galleria Mellonella ◽  
Fungal Infections ◽  
Model Organisms ◽  
In Vivo Models ◽  
Alternative Models ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Malassezia Spp

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated with the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host–microbe interactions of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review, we present different models that have been implemented in fungal infections studies with greater attention to Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host–microbe interactions. This is due to the fact that these systems have been shown to have reliable results, which correlate with those obtained from mammalian models. Examples of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

scholarly journals In vitro antifungal activity of Candida culture extracts against Trichophyton rubrum and Trichophyton mentagrophytes.

2021 ◽  
Vol 1 (4) ◽  
pp. 135-152
Author(s):  
Thiago Henrique Lemes ◽  
Guilherme Silva Torrezan ◽  
Carlos Roberto Polaquini ◽  
Luis Octavio Regasini ◽  
Bianca Gottardo de Almeida ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Galleria Mellonella ◽  
Trichophyton Rubrum ◽  
Fungal Infections ◽  
Trichophyton Mentagrophytes ◽  
Recurrence Rates ◽  
Isolation And Identification ◽  
Microdilution Method ◽  
Broth Microdilution Method

Onychomycoses are nail infections caused primarily by dermatophytes fungi, yeasts, and other filamentous fungi, characterized by persistent infections, prolonged therapy, and high recurrence rates. In clinical practice, some of these occurrences present two or more microorganisms, and the interactions among them can change the chemical environment mediated by small diffusible molecules, producing a competitive niche. The aim of this study was to evaluate the antifungal activity of individual extracts of pure cultures of Candida albicans and C. parapsilosis against dermatophytes. To obtain the fungal extracts, cultures were filtered through a 0.2 μm membrane and submitted to liquid-liquid extraction using ethyl acetate. The Minimal Inhibitory Concentration (MIC) of each extract was evaluated by broth microdilution method and checkerboard assay with fluconazole against clinical isolates of Trichophyton rubrum and T. mentagrophytes. The invertebrate model of Galleria mellonella was used to evaluate the toxicity of the extracts. As results, the extracts of C. albicans and C. parapsilosis showed antifungal activity with MICs between 31,2 – 2000 μg/mL. In association with fluconazole, synergistic effect was detected for all combinations. The extracts presented low toxicity in G. mellonella. In the future, isolation and identification of the extract compounds may allow new therapeutic approaches in the control of fungal infections.

scholarly journals Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

2015 ◽  
Vol 14 (8) ◽  
pp. 834-844 ◽  
Author(s):  
Ranjith Rajendran ◽  
Elisa Borghi ◽  
Monica Falleni ◽  
Federica Perdoni ◽  
Delfina Tosi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Inflammatory Responses ◽  
Fungal Infections ◽  
Infection Model ◽  
Content Type

ABSTRACT Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo . In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections.

Amphotericin B Loaded Nanostructured Lipid Carriers for Parenteral Delivery: Characterization, Antifungal and In vitro Toxicity Assessment

2019 ◽  
Vol 16 (7) ◽  
pp. 645-653 ◽  
Author(s):  
Pataranapa Nimtrakul ◽  
Waree Tiyaboonchai ◽  
Supaporn Lamlertthon
Keyword(s):  
Amphotericin B ◽  
Fungal Infections ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Aqueous Solubility ◽  
Toxicity Assessment ◽  
Nanostructured Lipid Carriers ◽  
In Vitro Toxicity ◽  
Drug Release Profile

Background: Amphotericin B (AmB) is important for the treatment of systemic fungal infections. Nowadays, only intravenous administration (IV) of AmB has been available due to its low aqueous solubility. Two forms of AmB are available. The first is Fungizone®, a mixture of AmB and sodium deoxcycholate that produces severe nephrotoxicity. The second are lipid-based formulations that reduce nephrotoxicity, but they are costly and require higher dose than Fungizone®. Thus, a cheaper delivery system with reduced AmB toxicity is required. Objective: To develop and characterize AmB loaded-nanostructured lipid carriers (AmB-loaded NLCs) for IV administration to reduce AmB toxicity. Methods: AmB-loaded NLCs with different solid lipids were prepared by the high-pressure homogenization technique. Their physicochemical properties and the drug release profile were examined. The molecular structure of AmB, antifungal and hemolysis activities of developed AmB-loaded NLCs were also evaluated. Results: AmB-loaded NLCs ~110 to ~140 nm in diameter were successfully produced with a zeta potential of ~-19 mV and entrapment efficiency of ~75%. In vitro release showed fast release characteristics. AmB-loaded NLCs could reduce the AmB molecular aggregation as evident from the absorbance ratio of the first to the fourth peak showing a partial aggregation of AmB. This result suggested that AmB-loaded NLCs could offer less nephrotoxicity compared to Fungizone®. In vitro antifungal activity of AmB-loaded NLCs showed a minimum inhibitory concentration of 0.25 µgmL-1. Conclusion: AmB-loaded NLCs present high potential carriers for effective IV treatment with prolonged circulation time and reduced toxicity.

scholarly journals Galleria mellonella for the Evaluation of Antifungal Efficacy against Medically Important Fungi, a Narrative Review

2020 ◽  
Vol 8 (3) ◽  
pp. 390 ◽  
Author(s):  
Sana Jemel ◽  
Jacques Guillot ◽  
Kalthoum Kallel ◽  
Françoise Botterel ◽  
Eric Dannaoui
Keyword(s):  
Fungal Pathogens ◽  
Galleria Mellonella ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Development Of Resistance ◽  
Antifungal Efficacy

The treatment of invasive fungal infections remains challenging and the emergence of new fungal pathogens as well as the development of resistance to the main antifungal drugs highlight the need for novel therapeutic strategies. Although in vitro antifungal susceptibility testing has come of age, the proper evaluation of therapeutic efficacy of current or new antifungals is dependent on the use of animal models. Mammalian models, particularly using rodents, are the cornerstone for evaluation of antifungal efficacy, but are limited by increased costs and ethical considerations. To circumvent these limitations, alternative invertebrate models, such as Galleria mellonella, have been developed. Larvae of G. mellonella have been widely used for testing virulence of fungi and more recently have proven useful for evaluation of antifungal efficacy. This model is suitable for infection by different fungal pathogens including yeasts (Candida, Cryptococcus, Trichosporon) and filamentous fungi (Aspergillus, Mucorales). Antifungal efficacy may be easily estimated by fungal burden or mortality rate in infected and treated larvae. The aim of the present review is to summarize the actual data about the use of G. mellonella for testing the in vivo efficacy of licensed antifungal drugs, new drugs, and combination therapies.

scholarly journals Silver(I) and Copper(II) Complexes of 1,10-Phenanthroline-5,6-Dione Against Phialophora verrucosa: A Focus on the Interaction With Human Macrophages and Galleria mellonella Larvae

2021 ◽  
Vol 12 ◽  
Author(s):  
Marcela Q. Granato ◽  
Thaís P. Mello ◽  
Renata S. Nascimento ◽  
Marcos D. Pereira ◽  
Thabatta L. S. A. Rosa ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Human Macrophages ◽  
Phialophora Verrucosa ◽  
Dematiaceous Fungus

Phialophora verrucosa is a dematiaceous fungus that causes mainly chromoblastomycosis, but also disseminated infections such as phaeohyphomycosis and mycetoma. These diseases are extremely hard to treat and often refractory to current antifungal therapies. In this work, we have evaluated the effect of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based complexes, [Ag (phendione)2]ClO4 and [Cu(phendione)3](ClO4)2.4H2O, against P. verrucosa, focusing on (i) conidial viability when combined with amphotericin B (AmB); (ii) biofilm formation and disarticulation events; (iii) in vitro interaction with human macrophages; and (iv) in vivo infection of Galleria mellonella larvae. The combination of AmB with each of the test compounds promoted the additive inhibition of P. verrucosa growth, as judged by the checkerboard assay. During the biofilm formation process over polystyrene surface, sub-minimum inhibitory concentrations (MIC) of phendione and its silver(I) and copper(II) complexes were able to reduce biomass and extracellular matrix production. Moreover, a mature biofilm treated with high concentrations of the test compounds diminished biofilm viability in a concentration-dependent manner. Pre-treatment of conidial cells with the test compounds did not alter the percentage of infected THP-1 macrophages; however, [Ag(phendione)2]ClO4 caused a significant reduction in the number of intracellular fungal cells compared to the untreated system. In addition, the killing process was significantly enhanced by post-treatment of infected macrophages with the test compounds. P. verrucosa induced a typically cell density-dependent effect on G. mellonella larvae death after 7 days of infection. Interestingly, exposure to the silver(I) complex protected the larvae from P. verrucosa infection. Collectively, the results corroborate the promising therapeutic potential of phendione-based drugs against fungal infections, including those caused by P. verrucosa.

A Short-term Bovine Sperm Cell Assay for the Evaluation of the In Vitro Cytotoxicity of Chemicals

1990 ◽  
Vol 17 (3) ◽  
pp. 228-232
Author(s):  
Hasso Seibert ◽  
Ulrich Gosch
Keyword(s):  
Test Procedure ◽  
In Vitro Cytotoxicity ◽  
In Vitro Toxicity ◽  
Cytotoxic Action ◽  
Response Patterns ◽  
Toxic Response ◽  
Modes Of Action ◽  
Bovine Spermatozoa ◽  
New Compounds

A test procedure is described for the use of ejaculated bovine spermatozoa in evaluating the in vitro cytotoxicity of chemicals. Results from experiments with model substances with known modes of action (inhibitors of mitochondrial electron transport, uncouplers of mitochondrial phosphorylation, surfactants, organic solvents) are presented and suggest that specific toxic-response patterns can be defined for the different modes of action. It is concluded that the in vitro toxicity profiles obtained in the assay described can be used for a first qualitative analysis of the cytotoxic action of little studied or new compounds, in addition to a quantitative assessment of their cytotoxic potency.

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