Carvacrol essential oil stimulates growth performance, immune response, and tolerance of Nile tilapia to Cryptococcus uniguttulatus infection

2020 ◽  
Vol 141 ◽  
pp. 1-14 ◽  
Author(s):  
HH Mahboub ◽  
YH Tartor
Keyword(s):  
Antifungal Activity ◽  
Growth Performance ◽  
Nile Tilapia ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Fish Growth ◽  
Immunological Parameters ◽  
Species Production

This study investigated the antifungal activity of 5 essential oils (EOs) towards yeasts recovered from diseased fishes; and focused on the efficacy of one EO (carvacrol) on growth performance, non-specific immunity, and disease resistance of Nile tilapia Oreochromis niloticus against Cryptococcus uniguttulatus challenge. Thymoquinone, thymol, carvacrol, eugenol, and cinnamon were first tested in vitro against 20 clinical yeast strains in comparison with antifungal drugs (fluconazole, ketoconazole, itraconazole, amphotericin B, nystatin, and clotrimazole) using disc diffusion and broth microdilution methods. For the in vivo challenge, fish (n = 150) were divided into 5 groups (carvacrol prophylaxis, carvacrol treatment, itraconazole treatment, unchallenged control, and positive control; 30 fish group-1) with 3 replicates. Phagocytic activity, reactive oxygen species production, reactive nitrogen species production, myeloperoxidase, lysozyme activity, and total immunoglobulins were tested before and after challenge. Relative percent survival (RPS) and mortality percent were determined as indicators for functional immunity. EOs displayed divergent degrees of antifungal activity, and carvacrol was the most effective against the tested yeasts. The dietary additive of carvacrol significantly enhanced growth performance, all immunological parameters, and the RPS values (90%) compared to other treatments. This unique experimental model indicates that carvacrol seems promising not only for enhancing immunity and promoting fish growth, but also for controlling emerging fungal infections. Future studies should investigate different concentrations of carvacrol as well as its antifungal activity in different fish species.

scholarly journals Poly-ε-caprolactone Nanoparticles Loaded with 4-Nerolidylcatechol (4-NC) for Growth Inhibition of Microsporum canis

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 894
Author(s):  
Vanessa Raquel Greatti ◽  
Fernando Oda ◽  
Rodrigo Sorrechia ◽  
Bárbara Regina Kapp ◽  
Carolina Manzato Seraphim ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Growth Inhibition ◽  
Fungal Infections ◽  
Polymeric Nanoparticles ◽  
Weight Ratio ◽  
Microsporum Canis ◽  
Nanostructured Systems ◽  
The Stability

Dermatophyte fungal infections are difficult to treat because they need long-term treatments. 4-Nerolidylcatechol (4-NC) is a compound found in Piper umbellatum that has been reported to demonstrate significant antifungal activity, but is easily oxidizable. Due to this characteristic, the incorporation in nanostructured systems represents a strategy to guarantee the compound’s stability compared to the isolated form and the possibility of improving antifungal activity. The objective of this study was to incorporate 4-NC into polymeric nanoparticles to evaluate, in vitro and in vivo, the growth inhibition of Microsporum canis. 4-NC was isolated from fresh leaves of P. umbellatum, and polymer nanoparticles of polycaprolactone were developed by nanoprecipitation using a 1:5 weight ratio (drug:polymer). Nanoparticles exhibited excellent encapsulation efficiency, and the antifungal activity was observed in nanoparticles with 4-NC incorporated. Polymeric nanoparticles can be a strategy employed for decreased cytotoxicity, increasing the stability and solubility of substances, as well as improving the efficacy of 4-NC.

scholarly journals Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy for fungal infections

2018 ◽  
Vol 5 (3) ◽  
pp. 171814 ◽  
Author(s):  
Chang Shu ◽  
Tengfei Li ◽  
Wen Yang ◽  
Duo Li ◽  
Shunli Ji ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Water Soluble ◽  
Naphthalene Acetic Acid ◽  
Innovative Strategy ◽  
Molecular Arrangement

The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans . The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.

scholarly journals Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Visesato Mor ◽  
Antonella Rella ◽  
Amir M. Farnoud ◽  
Ashutosh Singh ◽  
Mansa Munshi ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Sequencing Analysis ◽  
Fungal Cell ◽  
New Class ◽  
Narrow Spectrum

ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. IMPORTANCE Fungal infections are a significant cause of morbidity and mortality worldwide. Current antifungal drugs suffer from various drawbacks, including toxicity, drug resistance, and narrow spectrum of activity. In this study, we have demonstrated that pharmaceutical inhibition of fungal glucosylceramide presents a new opportunity to treat cryptococcosis and various other fungal infections. In addition to being effective against pathogenic fungi, the compounds discovered in this study were well tolerated by animals and additive to current antifungals. These findings suggest that these drugs might pave the way for the development of a new class of antifungals.

scholarly journals Miltefosine Against Scedosporium and Lomentospora Species: Antifungal Activity and Its Effects on Fungal Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Rodrigo Rollin-Pinheiro ◽  
Yuri de Castro Almeida ◽  
Victor Pereira Rochetti ◽  
Mariana Ingrid Dutra da Silva Xisto ◽  
Luana Pereira Borba-Santos ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Membrane Integrity ◽  
Antifungal Drugs ◽  
Mitochondrial Activity ◽  
Clinical Settings ◽  
Fungal Cell ◽  
Wide Range ◽  
Exogenous Addition ◽  
Species Production

Scedosporium and Lomentospora species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising conditions. Because they are usually resistant to many antifungal drugs available in clinical settings, studies of alternative targets in fungal cells and therapeutic approaches are necessary. In the present work, we evaluated the in vitro antifungal activity of miltefosine against Scedosporium and Lomentospora species and how this phospholipid analogue affects the fungal cell. Miltefosine inhibited different Scedosporium and Lomentospora species at 2–4 µg/ml and reduced biofilm formation. The loss of membrane integrity in Scedosporium aurantiacum caused by miltefosine was demonstrated by leakage of intracellular components and lipid raft disorganisation. The exogenous addition of glucosylceramide decreased the inhibitory activity of miltefosine. Reactive oxygen species production and mitochondrial activity were also affected by miltefosine, as well as the susceptibility to fluconazole, caspofungin and myoricin. The data obtained in the present study contribute to clarify the dynamics of the interaction between miltefosine and Scedosporium and Lomentospora cells, highlighting its potential use as new antifungal drug in the future.

scholarly journals Non-toxic Cobalt(III) Schiff Base Complexes with Broad Spectrum Antifungal Activity

2020 ◽  
Author(s):  
Angelo Frei ◽  
A. Paden King ◽  
Gabrielle J. Lowe ◽  
Amy K. Cain ◽  
Francesca L. Short ◽  
...  
Keyword(s):  
Schiff Base ◽  
Antifungal Activity ◽  
Broad Spectrum ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Schiff Base Complexes ◽  
In Vivo Studies

Resistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug resistant fungal infections, with only a handful of new drugs currently in development. Given that metal complexes have proven to be useful new chemotypes in the fight against diseases such as cancer, malaria, and bacterial infections, it stands to reason to explore their possible utility in treating fungal infections. Herein we report a series of cobalt(III) Schiff base complexes with broad spectrum antifungal activity. Some of these complexes (1-3) show minimum inhibitory concentrations (MIC) in the low micro- to nanomolar range against a series of Candida and Cryptococcus yeasts. Additionally, we demonstrate that these compounds show no cytotoxicity against both bacterial and human cells. Finally, we report first in vivo toxicity data on these compounds in Galleria mellonella, showing that doses as high as 266 mg/kg are tolerated without adverse effects, paving the way for further in vivo studies of these complexes. <br>

scholarly journals Antifungal effect of all-trans retinoic acid against Aspergillus fumigatus in vitro and in a pulmonary aspergillosis in vivo model

2020 ◽  
Author(s):  
Elena Campione ◽  
Roberta Gaziano ◽  
Elena Doldo ◽  
Daniele Marino ◽  
Mattia Falconi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Aspergillus Fumigatus ◽  
Rat Model ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Antifungal Drugs ◽  
Pulmonary Aspergillosis ◽  
Fungistatic Activity

AIM: Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. Fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro. We evaluated the efficacy of ATRA in vivo and its potential synergistic interaction with other antifungal drugs. MATERIALS AND METHODS: A rat model of IPA and in vitro experiments were performed to assess the efficacy of ATRA against Aspergillus in association with classical antifungal drugs and in silico studies used to clarify its mechanism of action. RESULTS: ATRA (0.5 and 1 mM) displayed a strong fungistatic activity in Aspergillus cultures, while at lower concentrations, synergistically potentiated fungistatic efficacy of sub-inhibitory concentration of Amphotericin B (AmB) and Posaconazole (POS). ATRA also enhanced macrophagic phagocytosis of conidia. In a rat model of IPA, ATRA reduced mortality similarly to Posaconazole. CONCLUSION: Fungistatic efficacy of ATRA alone and synergistically with other antifungal drugs was documented in vitro, likely by inhibiting fungal Hsp90 expression and Hsp90-related genes. ATRA reduced mortality in a model of IPA in vivo. Those findings suggest ATRA as suitable fungistatic agent, also to reduce dosage and adverse reaction of classical antifungal drugs, and new therapeutic strategies against IPA and systemic fungal infections.

scholarly journals Antifungal In Vitro Activity of Pilosulin- and Ponericin-Like Peptides from the Giant Ant Dinoponera quadriceps and Synergistic Effects with Antimycotic Drugs

Antibiotics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 354 ◽  
Author(s):  
Hilania Valéria Dodou Lima ◽  
Carolina Sidrim de Paula Cavalcante ◽  
Gandhi Rádis-Baptista
Keyword(s):  
Antifungal Activity ◽  
Antimicrobial Peptides ◽  
Broad Spectrum ◽  
Culture Medium ◽  
Fungal Infections ◽  
Synergistic Effects ◽  
Antifungal Drugs ◽  
Clinical Strain ◽  
Onset Of Action

Venoms from ants comprise a rich source of bioactive peptides, including antimicrobial peptides. From the proteome and peptidome of the giant ant Dinoponera quadriceps venom, members of five known classes of antimicrobial peptides were disclosed (e.g., dermaseptin-, defensin-, ICK-, pilosulin- and ponericin-like types). Based on comparative analysis, these family members have structural determinants that indicate they could display antimicrobial activities. In previous works, pilosulin- and ponericin-like peptides were demonstrated to be active against bacteria, fungi, and parasites. Herein, the antifungal activity of ponericin- and pilosulin-like peptides were assessed, aiming at the expansion of the knowledge about AMPs in predatory ants and the development of new microbicide strategies to deal with difficult-to-treat fungal infections. Synthetic pilosulin- (Dq-2562, Dq-1503, and Dq-1319) and ponericin-like (Dq-3162) peptides were evaluated for their fungicide and fungistatic activities against different species of Candida, including a drug-resistant clinical strain. The MICs and MLCs were determined for all peptides individually and in combination with general antifungal drugs by the microdilution method. The time-kill kinetic curves were set up by means of a luminescent reagent, of which the light signal is proportional to the number of viable cells. The candicidal synergism observed by the combination of subinhibitory concentrations of peptides and general antimycotic drugs were quantified by the checkerboard test and fluorescent dye permeation assay. The influence of ergosterol on the antifungal activity was verified by supplementation of culture medium. The pilosulin- (Dq-2562 and Dq-1503) and ponericin-like (Dq-3162) were the most active peptides, displaying a broad spectrum of antifungal activity in vitro, with MICs in the range of 0.625 to 10 µM. The combination of peptides and conventional antimycotic drugs displayed a synergistic reduction in the MIC values of individual peptides and drugs, while soluble ergosterol in the culture medium increased the MICs. The fungicide and fungistatic activity of the individual peptides and peptides in combination with antimycotics were time-dependent with a rapid onset of action and long-lasting effect, which involved membrane disruption as an underlying mechanism of their action. Altogether, pilosulin- and ponericin-like peptides from the giant ant D. quadriceps venom display a broad-spectrum of candicidal activity, what allows their inclusion in the row of the antifungal peptides and gives support for further studies on the development of strategies to fight candidiasis.

scholarly journals Natural Killer Cells and Antifungal Host Response

2013 ◽  
Vol 20 (4) ◽  
pp. 452-458 ◽  
Author(s):  
Stanislaw Schmidt ◽  
Stefanie-Yvonne Zimmermann ◽  
Lars Tramsen ◽  
Ulrike Koehl ◽  
Thomas Lehrnbecher
Keyword(s):  
Antifungal Activity ◽  
Nk Cells ◽  
Natural Killer ◽  
Host Response ◽  
Fungal Infections ◽  
Treatment Strategies ◽  
Cytotoxic Molecules ◽  
Insight Into

ABSTRACTAs a result of improved experimental methodologies and a better understanding of the immune system, there is increasing insight into the antifungal activity of natural killer (NK) cells. Murine and human NK cells are able to damage fungi of different genera and speciesin vitro, and they exert both direct and indirect antifungal activity through cytotoxic molecules such as perforin and through cytokines and interferons, respectively. On the other hand, recent data suggest that fungi exhibit immunosuppressive effects on NK cells. Whereas clearin vivodata are lacking in humans, the importance of NK cells in the host response against fungi has been demonstrated in animal models. Further knowledge of the interaction of NK cells with fungi might help to better understand the pathogenesis of invasive fungal infections and to improve treatment strategies.

scholarly journals The celecoxib derivative AR-12 has broad spectrum antifungal activity in vitro and improves the activity of fluconazole in a murine model of cryptococcosis

2016 ◽  
pp. AAC.01061-16 ◽  
Author(s):  
Kristy Koselny ◽  
Julianne Green ◽  
Louis DiDone ◽  
Justin P. Halterman ◽  
Annette W. Fothergill ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Small Molecules ◽  
Broad Spectrum ◽  
Murine Model ◽  
Antifungal Drugs ◽  
Dimorphic Fungi ◽  
New Class ◽  
Cancer Agent

Only one new class of antifungal drugs has been introduced into clinical practice in the last thirty years and, thus, the identification of small molecules with novel mechanisms of action is an important goal of current anti-infective research. Here, we describe the characterization of the spectrum of in vitro activity and in vivo activity of AR-12, a celecoxib-derivative which has been tested in a Phase I clinical trial as an anti-cancer agent. AR-12 inhibits fungal acetyl CoA synthetase in vitro and is fungicidal at concentrations similar to those achieved in human plasma. AR-12 has a broad spectrum of activity including active against yeasts (e.g.,C. albicans, non-albicansCandidaspp.,C. neoformans); molds (e.g.,Fusarium,Mucor), and dimorphic fungi (Blastomyces,Histoplasma, andCoccidioides) with minimum inhibitory concentrations of 2-4 μg/mL. AR-12 is also active against azole- and echinocandin-resistantCandidaisolates and sub-inhibitory AR-12 concentrations increase susceptibility of fluconazole- and echinocandin-resistantCandidaisolates. Finally, AR-12 also increases the activity of fluconazole in a murine model of cryptococcosis. Taken together, these data indicate that AR-12 represents a promising class of small molecules with broad spectrum antifungal activity.

Preparation, characterizations and evaluation of antifungal activity of eugenol-linalool emulgel against anthrophilic dermatophytic trichophyton rubrum

2021 ◽  
pp. 1-15
Author(s):  
Abdullah Akram ◽  
Muhammad Khalid Khan ◽  
Barkat Ali Khan
Keyword(s):  
Antifungal Activity ◽  
Skin Infection ◽  
Trichophyton Rubrum ◽  
Sem Analysis ◽  
Antifungal Drugs ◽  
In Vivo Studies ◽  
Stability Studies ◽  
Antifungal Activities

Trichophyton rubrum (T. Rubrum) is responsible for chronic cases of dermatophytosis which have high rates of resistance to antifungal drugs worldwide. The aim of this study was to formulate an emulgel of Eugenol-Linalool for the treatment of T. Rubrum infections. The emulgel was prepared by slow emulsification method and characterized for physical examination, pH analysis, swelling index, stability studies, spreading coefficient, SEM analysis, thermal analysis and PXRD studies. In-vitro antifungal activities were performed by growing T. rubrum on specialized media in petri dishes. In-vivo antifungal activity was performed in rabbits by inducing the skin infection by application of fungal strain. Results indicated that the emulgel formulation is highly stable and the physical properties of the emulgel remained quite feasible. No deterioration was observed in the formulation and the pH remained the same as the pH of skin. The viscosity and spreadability of the emulgel remained highly compatible. The results of in vitro and in vivo studies indicated that the Eugenol and Linalool both inhibited the growth of T. rubrum. Eugenol was more effective in inhibition of zone (38±0.01 mm) of T. rubrum as compared to Linalool (32.9±0.03 mm). Similarly it was observed that when the combination of both Linalool and Eugenol was used, the growth of T. rubrum (42±0.01 mm) was significantly (P <  0.05) inhibited. It is hence concluded that the emulgel containing Eugenol and Linalool possess strong in vitro and in vivo antifungal activities against the commercial strains of anthrophilic dermophytic T. Rubrum.

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