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

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.

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

Diseases of Aquatic Organisms ◽

10.3354/dao03506 ◽

2020 ◽

Vol 141 ◽

pp. 1-14 ◽

Cited By ~ 1

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.

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Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine

Molecules ◽

10.3390/molecules25051079 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1079 ◽

Cited By ~ 1

Author(s):

Andreea-Iulia Pricopie ◽

Monica Focșan ◽

Ioana Ionuț ◽

Gabriel Marc ◽

Laurian Vlase ◽

...

Keyword(s):

Bovine Serum ◽

Membrane Integrity ◽

Antifungal Drugs ◽

Thiazole Derivatives ◽

Molecular Docking Study ◽

Binding Interaction ◽

Fungal Cell ◽

Broth Microdilution Method

Herein we report the synthesis of two novel series of 1,3-thiazole derivatives having a lipophilic C4-substituent on account of the increasing need for novel and versatile antifungal drugs for the treatment of resistant Candida sp.-based infections. Following their structural characterization, the anti-Candida activity was evaluated in vitro while using the broth microdilution method. Three compounds exhibited lower Minimum Inhibitory Concentration (MIC) values when compared to fluconazole, being used as the reference antifungal drug. An in silico molecular docking study was subsequently carried out in order to gain more insight into the antifungal mechanism of action, while using lanosterol-C14α-demethylase as the target enzyme. Fluorescence microscopy was employed to further investigate the cellular target of the most promising molecule, with the obtained results confirming its damaging effect towards the fungal cell membrane integrity. Finally, the distribution and the pharmacological potential in vivo of the novel thiazole derivatives was investigated through the study of their binding interaction with bovine serum albumin, while using fluorescence spectroscopy.

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In Vitro Synergistic Interactions of Isavuconazole and Echinocandins against Candida auris

Antibiotics ◽

10.3390/antibiotics10040355 ◽

2021 ◽

Vol 10 (4) ◽

pp. 355

Author(s):

Unai Caballero ◽

Sarah Kim ◽

Elena Eraso ◽

Guillermo Quindós ◽

Valvanera Vozmediano ◽

...

Keyword(s):

Interaction Model ◽

Antifungal Drugs ◽

Health Concern ◽

Candida Auris ◽

Fungistatic Activity ◽

Drug Concentrations ◽

Low Concentrations ◽

Wide Range ◽

Time Kill

Candida auris is an emergent fungal pathogen that causes severe infectious outbreaks globally. The public health concern when dealing with this pathogen is mainly due to reduced susceptibility to current antifungal drugs. A valuable alternative to overcome this problem is to investigate the efficacy of combination therapy. The aim of this study was to determine the in vitro interactions of isavuconazole with echinocandins against C. auris. Interactions were determined using a checkerboard method, and absorbance data were analyzed with different approaches: the fractional inhibitory concentration index (FICI), Greco universal response surface approach, and Bliss interaction model. All models were in accordance and showed that combinations of isavuconazole with echinocandins resulted in an overall synergistic interaction. A wide range of concentrations within the therapeutic range were selected to perform time-kill curves. These confirmed that isavuconazole–echinocandin combinations were more effective than monotherapy regimens. Synergism and fungistatic activity were achieved with combinations that included isavuconazole in low concentrations (≥0.125 mg/L) and ≥1 mg/L of echinocandin. Time-kill curves revealed that once synergy was achieved, combinations of higher drug concentrations did not improve the antifungal activity. This work launches promising results regarding the combination of isavuconazole with echinocandins for the treatment of C. auris infections.

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In Vitro Antifungal Activity of (1)-N-2-Methoxybenzyl-1,10-phenanthrolinium Bromide against Candida albicans and Its Effects on Membrane Integrity

Mycobiology ◽

10.5941/myco.2017.45.1.25 ◽

2017 ◽

Vol 45 (1) ◽

pp. 25-30 ◽

Cited By ~ 2

Author(s):

Setiawati Setiawati ◽

Titik Nuryastuti ◽

Ngatidjan Ngatidjan ◽

Mustofa Mustofa ◽

Jumina Jumina ◽

...

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Membrane Integrity ◽

In Vitro Antifungal Activity

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Hevein-Like Antimicrobial Peptides Wamps: Structure–Function Relationship in Antifungal Activity and Sensitization of Plant Pathogenic Fungi to Tebuconazole by WAMP-2-Derived Peptides

International Journal of Molecular Sciences ◽

10.3390/ijms21217912 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7912 ◽

Cited By ~ 3

Author(s):

Tatyana Odintsova ◽

Larisa Shcherbakova ◽

Marina Slezina ◽

Tatyana Pasechnik ◽

Bakhyt Kartabaeva ◽

...

Keyword(s):

Antifungal Activity ◽

Antimicrobial Peptides ◽

Structure Function ◽

Spore Germination ◽

Pathogenic Fungi ◽

Plant Pathogenic Fungi ◽

Fungal Cell ◽

Structure Function Relationship ◽

Function Relationship

Hevein-like antimicrobial peptides (AMPs) comprise a family of plant AMPs with antifungal activity, which harbor a chitin-binding site involved in interactions with chitin of fungal cell walls. However, the mode of action of hevein-like AMPs remains poorly understood. This work reports the structure–function relationship in WAMPs—hevein-like AMPs found in wheat (Triticum kiharae Dorof. et Migush.) and later in other Poaceae species. The effect of WAMP homologues differing at position 34 and the antifungal activity of peptide fragments derived from the central, N- and C-terminal regions of one of the WAMPs, namely WAMP-2, on spore germination of different plant pathogenic fungi were studied. Additionally, the ability of WAMP-2-derived peptides to potentiate the fungicidal effect of tebuconazole, one of the triazole fungicides, towards five cereal-damaging fungi was explored in vitro by co-application of WAMP-2 fragments with Folicur® EC 250 (25% tebuconazole). The antifungal activity of WAMP homologues and WAMP-2-derived peptides varied depending on the fungus, suggesting multiple modes of action for WAMPs against diverse pathogens. Folicur® combined with the WAMP-2 fragments inhibited the spore germination at a much greater level than the fungicide alone, and the type of interactions was either synergistic or additive, depending on the target fungus and concentration combinations of the compounds. The combinations, which resulted in synergism and drastically enhanced the sensitivity to tebuconazole, were revealed for all five fungi by a checkerboard assay. The ability to synergistically interact with a fungicide and exacerbate the sensitivity of plant pathogenic fungi to a commercial antifungal agent is a novel and previously uninvestigated property of hevein-like AMPs.

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Evaluation of Antifungal Activity and Mode of Action of New Coumarin Derivative, 7-Hydroxy-6-nitro-2H-1-benzopyran-2-one, againstAspergillusspp.

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/925096 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Felipe Queiroga Sarmento Guerra ◽

Rodrigo Santos Aquino de Araújo ◽

Janiere Pereira de Sousa ◽

Fillipe de Oliveira Pereira ◽

Francisco J. B. Mendonça-Junior ◽

...

Keyword(s):

Cell Wall ◽

Mode Of Action ◽

Cell Walls ◽

Coumarin Derivative ◽

Antifungal Drugs ◽

Azole Resistance ◽

Subinhibitory Concentration ◽

Fungal Cell ◽

Mycelia Growth

Aspergillusspp. produce a wide variety of diseases. For the treatment of such infections, the azoles and Amphotericin B are used in various formulations. The treatment of fungal diseases is often ineffective, because of increases in azole resistance and their several associated adverse effects. To overcome these problems, natural products and their derivatives are interesting alternatives. The aim of this study was to examine the effects of coumarin derivative, 7-hydroxy-6-nitro-2H-1-benzopyran-2-one (Cou-NO2), both alone and with antifungal drugs. Its mode of action againstAspergillusspp. Cou-NO2was tested to evaluate its effects on mycelia growth and germination of fungal conidia ofAspergillusspp. We also investigated possible Cou-NO2action on cell walls (0.8 M sorbitol) and on Cou-NO2to ergosterol binding in the cell membrane. The study shows that Cou-NO2is capable of inhibiting both the mycelia growth and germination of conidia for the species tested, and that its action affects the structure of the fungal cell wall. At subinhibitory concentration, Cou-NO2enhanced thein vitroeffects of azoles. Moreover, in combination with azoles (voriconazole and itraconazole) Cou-NO2displays an additive effect. Thus, our study supports the use of coumarin derivative 7-hydroxy-6-nitro-2H-1-benzopyran-2-one as an antifungal agent againstAspergillusspecies.

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In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.10.2503 ◽

1998 ◽

Vol 42 (10) ◽

pp. 2503-2510 ◽

Cited By ~ 58

Author(s):

Maurizio Del Poeta ◽

Wiley A. Schell ◽

Christine C. Dykstra ◽

Susan K. Jones ◽

Richard R. Tidwell ◽

...

Keyword(s):

Antimicrobial Activity ◽

Candida Albicans ◽

Fusarium Solani ◽

Antifungal Agents ◽

Antifungal Drugs ◽

Inhibitory Compounds ◽

Wide Range ◽

Fluconazole Resistant ◽

Resistant Strains

ABSTRACT Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities againstCandida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 μg/ml, and it was the most potent compound against C. neoformans (MIC, ≤0.09 μg/ml). Selected compounds were also found to be active againstAspergillus fumigatus, Fusarium solani,Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.

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Application of Plant Extracts to Control Postharvest Gray Mold and Susceptibility of Apple Fruits to B. cinerea from Different Plant Hosts

Foods ◽

10.3390/foods9101430 ◽

2020 ◽

Vol 9 (10) ◽

pp. 1430 ◽

Cited By ~ 1

Author(s):

Lina Šernaitė ◽

Neringa Rasiukevičiūtė ◽

Alma Valiuškaitė

Keyword(s):

Antifungal Activity ◽

Fungal Pathogens ◽

Plant Protection ◽

Gray Mold ◽

Postharvest Disease ◽

Cinnamon Extract ◽

Wide Range ◽

Plant Hosts ◽

Apple Fruits

Sustainable plant protection can be applied on apples against fungal pathogens such as Botrytis cinerea (which is responsible for gray mold)—a significant global postharvest disease. This pathogen can affect a wide range of hosts; and fruits may have variable susceptibilities to B. cinerea from different plant hosts. New possibilities to control gray mold in food production are under demand due to the emergence of resistance against antifungal agents in fungal pathogens. Cinnamon, pimento, and laurel extracts were previously assessed for antifungal activities under in vitro conditions and were found to have the potential to be effective against postharvest gray mold. Therefore, this study aimed to investigate the antifungal activity of cinnamon, pimento, and laurel extracts in vitro and against postharvest gray mold on apples to determine the susceptibility of apple fruits to B. cinerea from different plant hosts, and to analyze the chemical composition of the extracts. Apples (cv. “Connell Red”) were treated with different concentrations of extracts and inoculated with B. cinerea isolates from apple and strawberry followed by evaluation of in vitro antifungal activity. The results reveal that most of the concentrations of the extracts that were investigated were not efficient enough when assessed in the postharvest assay, despite having demonstrated a high in vitro antifungal effect. Apples were less susceptible to B. cinerea isolated from strawberry. To conclude, cinnamon extract was found to be the most effective against apple gray mold; however, higher concentrations of the extracts are required for the efficient inhibition of B. cinerea in fruits during storage.

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Chromoblastomykose: Mit der Kombination aus PDT und Antimykotika zum Erfolg

Karger Kompass Dermatologie ◽

10.1159/000507001 ◽

2020 ◽

Vol 8 (2) ◽

pp. 68-69

Author(s):

Percy Lehmann

Keyword(s):

Aminolevulinic Acid ◽

Southern China ◽

Antifungal Drugs ◽

Dematiaceous Fungi ◽

Promising Alternative ◽

Causative Agents ◽

Chronic Skin ◽

Species Production ◽

Complex Cases

Background: Chromoblastomycosis is a chronic skin and subcutaneous fungal infection caused by dematiaceous fungi and is associated with low cure and high relapse rates. In southern China, Fonsecaea monophora and Fonsecaea pedrosoi are the main causative agents. Principal findings: We treated 5 refractory and complex cases of chromoblastomycosis with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with oral antifungal drugs. The lesions improved after 4 to 9 sessions of ALA-PDT treatment at an interval of one or two weeks, and in some cases, mycological testing results became negative. The isolates were assayed for susceptibility to antifungal drugs and ALA-PDT in vitro, revealing sensitivity to terbinafine, itraconazole and voriconazole, with ALA-PDT altering the cell wall and increasing reactive oxygen species production. Conclusions: These results provide the basis for the development of a new therapeutic approach, and ALA-PDT combined with oral antifungal drugs constitutes a promising alternative method for the treatment of refractory and complex cases of chromoblastomycosis.

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Two Polyketides Produced by Endophytic Penicillium citrinum DBR-9 From Medicinal Plant Stephania kwangsiensis and Their Antifungal Activity Against Plant Pathogenic Fungi

Natural Product Communications ◽

10.1177/1934578x19846795 ◽

2019 ◽

Vol 14 (5) ◽

pp. 1934578X1984679 ◽

Cited By ~ 2

Author(s):

Haiyu Luo ◽

Zhen Qing ◽

Yecheng Deng ◽

Zhiyong Deng ◽

Xia’an Tang ◽

...

Keyword(s):

Medicinal Plant ◽

Membrane Integrity ◽

Pathogenic Fungi ◽

Significant Inhibition ◽

Penicillium Citrinum ◽

Plant Pathogenic Fungi ◽

Fungal Cell ◽

Cell Membrane Integrity ◽

Chinese Medicinal Plant

Endophytic fungi, especially those found in medicinal plants, are widely studied as producers of secondary metabolites of biotechnological interest. In this study, on the basis of an activity-directed isolation method and spectroscopic analysis, two active polyketides, citrinin (1) and emodin (2), were isolated and identified from the fermentation of the endophytic fungus Penicillium citrinum DBR-9. This fungus was isolated from the root tubers of the traditional Chinese medicinal plant Stephania kwangsiensis. In vitro antifungal assay showed that the two polyketides displayed significant inhibition on hypha growth of tested plant pathogenic fungi with IC50 values ranging from 3.1 to 123.1 μg/mL and 3.0 to 141.0 μg/mL, respectively. In addition, the mechanism of the effects of emodin (2) on the pathogen revealed it could affect the colony morphology, destroy cell membrane integrity, and influence the protein synthesis of the tested fungal cell. This work is the first report of two polyketides-producing endophytic P. citrinum DBR-9 from the medicinal plant S. kwangsiensis. Our results present new opportunities to deeply understand the potential of these two polyketides as natural antifungal agents to control phytopathogens in agriculture.

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