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Special Issue "Synthetic and Natural Antifungals—Desirable and Hazardous Effects"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 31 January 2022.

Special Issue Editors

Dr. Dejan Stojković
E-Mail Website
Guest Editor
Mycological laboratory, Department of Plant Physiology, Institute for Biological Research "Siniša Stanković"—National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia
Interests: mushrooms; mycomedicines; mycofood
Special Issues and Collections in MDPI journals
Dr. Marija Ivanov
E-Mail
Guest Editor
Institute for Biological Research "Siniša Stanković"—National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia
Dr. Ana Ćirić
E-Mail
Guest Editor
Institute for Biological Research "Siniša Stanković"—National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia

Special Issue Information

Dear Colleagues,

More than a billion people are suffering from various fungal infections, with more than 1.5 million having fatal consequences. These infections are difficult to treat, making the mortality rates high, even in the 21st century, despite the various antifungals that are currently available. Moreover, fungal biofilms are difficult to treat since they show resistance to the host immune system and conventional antifungal treatments when compared to free-floating cells.

This Special Issue will cover the following topics, including, but is not limited to:

*Synthetic and natural antifungals;

*Biocontrol of pathogenic fungi;

*Compounds acting as fungal biofilm inhibitors;

*Mechanisms of antifungal action;

*Mechanisms of fungal resistance to antifungals;

*Harmful effects of synthetic and natural fungicides;

*Beneficial health effects of natural antifungals and other biological effects.

Dr. Dejan Stojković
Dr. Marija Ivanov
Dr. Ana Ćirić
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Research

Article
The Influence of Tea Tree Oil on Antifungal Activity and Pharmaceutical Characteristics of Pluronic®F-127 Gel Formulations with Ketoconazole
by , and
Int. J. Mol. Sci. 2021, 22(21), 11326; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111326 (registering DOI) - 20 Oct 2021
Abstract
Fungal skin infections are currently a major clinical problem due to their increased occurrence and drug resistance. The treatment of fungal skin infections is based on monotherapy or polytherapy using the synergy of the therapeutic substances. Tea tree oil (TTO) may be a [...] Read more.
Fungal skin infections are currently a major clinical problem due to their increased occurrence and drug resistance. The treatment of fungal skin infections is based on monotherapy or polytherapy using the synergy of the therapeutic substances. Tea tree oil (TTO) may be a valuable addition to the traditional antifungal drugs due to its antifungal and anti-inflammatory activity. Ketoconazole (KTZ) is an imidazole antifungal agent commonly used as a treatment for dermatological fungal infections. The use of hydrogels and organogel-based formulations has been increasing for the past few years, due to the easy method of preparation and long-term stability of the product. Therefore, the purpose of this study was to design and characterize different types of Pluronic®F-127 gel formulations containing KTZ and TTO as local delivery systems that can be applied in cases of skin fungal infections. The influence of TTO addition on the textural, rheological, and bioadhesive properties of the designed formulations was examined. Moreover, the in vitro release of KTZ, its permeation through artificial skin, and antifungal activity by the agar diffusion method were performed. It was found that obtained gel formulations were non-Newtonian systems, showing a shear-thinning behaviour and thixotropic properties with adequate textural features such as hardness, compressibility, and adhesiveness. Furthermore, the designed preparations with TTO were characterized by beneficial bioadhesive properties. The presence of TTO improved the penetration and retention of KTZ through the artificial skin membrane and this effect was particularly visible in hydrogel formulation. The developed gels containing TTO can be considered as favourable formulations in terms of drug release and antifungal activity. Full article
(This article belongs to the Special Issue Synthetic and Natural Antifungals—Desirable and Hazardous Effects)
Article
Biological Control of Leaf Blight Disease Caused by Pestalotiopsis maculans and Growth Promotion of Quercus acutissima Carruth Container Seedlings Using Bacillus velezensis CE 100
by , , , , , and
Int. J. Mol. Sci. 2021, 22(20), 11296; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011296 (registering DOI) - 19 Oct 2021
Abstract
Leaf blight disease caused by Pestalotiopsismaculans lead to deleterious losses in the quality of forest container seedlings. The use of plant growth-promoting bacteria provides a promising strategy to simultaneously control diseases and enhance forest seedling production. This study investigated the biocontrol of [...] Read more.
Leaf blight disease caused by Pestalotiopsismaculans lead to deleterious losses in the quality of forest container seedlings. The use of plant growth-promoting bacteria provides a promising strategy to simultaneously control diseases and enhance forest seedling production. This study investigated the biocontrol of leaf blight disease and growth promotion potential of Bacillus velezensis CE 100 in Quercus acutissima Carruth seedlings. B. velezensis CE 100 produced cell wall degrading enzymes, such as chitinase, β-l,3-glucanase, and protease, which caused cell wall lysis and hyphae deformation of P. maculans, leading to mycelial growth inhibition by 54.94%. Inoculation of B. velezensis CE 100 suppressed P. maculans infection and increased seedling survival rate by 1.6-fold and 1.3-fold compared to chemical fertilizer and control, respectively. In addition, B. velezensis CE 100 produced indole-3-acetic acid, which improved root development and nutrient uptake compared to chemical fertilizer and control. Especially, inoculation with B. velezensis CE 100 increased the total nitrogen content of Q. acutissima seedlings, improved the chlorophyll index in the leaves, and increased seedling biomass by 1.3-fold and 2.2-fold compared to chemical fertilizer and control, respectively. Thus, B. velezensis CE 100 could be applied in the eco-friendly production of high-quality forest seedlings. Full article
(This article belongs to the Special Issue Synthetic and Natural Antifungals—Desirable and Hazardous Effects)
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Article
Fungicidal Activity and Mechanism of Action of Glabridin from Glycyrrhiza glabra L.
Int. J. Mol. Sci. 2021, 22(20), 10966; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222010966 - 11 Oct 2021
Viewed by 239
Abstract
Glycyrrhiza glabra (Licorice) belongs to the Fabaceae family and its extracts have exhibited significant fungicidal activity against phytopathogenic fungi, which has mainly been attributed to the presence of phenolic compounds such as flavonoids, isoflavonoids and chalcones. In this study, a series of licorice [...] Read more.
Glycyrrhiza glabra (Licorice) belongs to the Fabaceae family and its extracts have exhibited significant fungicidal activity against phytopathogenic fungi, which has mainly been attributed to the presence of phenolic compounds such as flavonoids, isoflavonoids and chalcones. In this study, a series of licorice flavonoids, isoflavonoids and chalcones were evaluated for their fungicidal activity against phytopathogenic fungi. Among them, glabridin exhibited significant fungicidal activity against ten kinds of phytopathogenic fungi. Notably, glabridin displayed the most active against Sclerotinia sclerotiorum with an EC50 value of 6.78 µg/mL and was 8-fold more potent than azoxystrobin (EC50, 57.39 µg/mL). Moreover, the in vivo bioassay also demonstrated that glabridin could effectively control S. sclerotiorum. The mechanism studies revealed that glabridin could induce reactive oxygen species accumulation, the loss of mitochondrial membrane potential and cell membrane destruction through effecting the expression levels of phosphatidylserine decarboxylase that exerted its fungicidal activity. These findings indicated that glabridin exhibited pronounced fungicidal activities against S. sclerotiorum and could be served as a potential fungicidal candidate. Full article
(This article belongs to the Special Issue Synthetic and Natural Antifungals—Desirable and Hazardous Effects)
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Article
The Antifungal Mechanism of Isoxanthohumol from Humulus lupulus Linn.
Int. J. Mol. Sci. 2021, 22(19), 10853; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910853 - 07 Oct 2021
Viewed by 253
Abstract
Humulus lupulus Linn. is a traditional medicinal and edible plant with several biological properties. The aims of this work were: (1) to evaluate the in vitro antifungal activity of H. lupulus ethanolic extract; (2) to study the in vitro and in vivo antifungal [...] Read more.
Humulus lupulus Linn. is a traditional medicinal and edible plant with several biological properties. The aims of this work were: (1) to evaluate the in vitro antifungal activity of H. lupulus ethanolic extract; (2) to study the in vitro and in vivo antifungal activity of isoxanthohumol, an isoprene flavonoid from H. lupulus, against Botrytis cinerea; and (3) to explore the antifungal mechanism of isoxanthohumol on B. cinerea. The present data revealed that the ethanolic extract of H. lupulus exhibited moderate antifungal activity against the five tested phytopathogenic fungi in vitro, and isoxanthohumol showed highly significant antifungal activity against B. cinerea, with an EC50 value of 4.32 µg/mL. Meanwhile, it exhibited moderate to excellent protective and curative efficacies in vivo. The results of morphologic observation, RNA-seq, and physiological indicators revealed that the antifungal mechanism of isoxanthohumol is mainly related to metabolism; it affected the carbohydrate metabolic process, destroyed the tricarboxylic acid (TCA) cycle, and hindered the generation of ATP by inhibiting respiration. Further studies indicated that isoxanthohumol caused membrane lipid peroxidation, thus accelerating the death of B. cinerea. This study demonstrates that isoxanthohumol can be used as a potential botanical fungicide for the management of phytopathogenic fungi. Full article
(This article belongs to the Special Issue Synthetic and Natural Antifungals—Desirable and Hazardous Effects)
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Article
Antifungal Activity of Bacillus velezensis CE 100 against Anthracnose Disease (Colletotrichum gloeosporioides) and Growth Promotion of Walnut (Juglans regia L.) Trees
Int. J. Mol. Sci. 2021, 22(19), 10438; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910438 - 28 Sep 2021
Viewed by 446
Abstract
Walnut anthracnose caused by Colletotrichum gloeosporioides is a deleterious disease that severely affects the production of walnut (Juglans regia L.). The aim of this study was to assess the antifungal and growth promotion activities of Bacillus velezensis CE 100 as an alternative [...] Read more.
Walnut anthracnose caused by Colletotrichum gloeosporioides is a deleterious disease that severely affects the production of walnut (Juglans regia L.). The aim of this study was to assess the antifungal and growth promotion activities of Bacillus velezensis CE 100 as an alternative to chemical use in walnut production. The crude enzyme from B. velezensis CE 100 exhibited chitinase, protease, and β-l,3-glucanase activity and degraded the cell wall of C. gloeosporioides, causing the inhibition of spore germination and mycelial growth by 99.3% and 33.6% at 100 µL/mL, respectively. The field application of B. velezensis CE 100 culture broth resulted in a 1.3-fold and 6.9-fold decrease in anthracnose disease severity compared to the conventional and control groups, respectively. Moreover, B. velezensis CE 100 produced indole-3-acetic acid (up to 1.4 µg/mL) and exhibited the potential for ammonium production and phosphate solubilization to enhance the availability of essential nutrients. Thus, field inoculation of B. velezensis CE 100 improved walnut root development, increased nutrient uptake, enhanced chlorophyll content, and consequently improved total biomass by 1.5-fold and 2.0-fold compared to the conventional and control groups, respectively. These results demonstrate that B. velezensis CE 100 is an effective biocontrol agent against anthracnose disease and a potential plant growth-promoting bacteria in walnut tree production. Full article
(This article belongs to the Special Issue Synthetic and Natural Antifungals—Desirable and Hazardous Effects)
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Article
Enhanced Fungicidal Efficacy by Co-Delivery of Azoxystrobin and Diniconazole with Cauliflower-Like Metal–Organic Frameworks NH2-Al-MIL-101
Int. J. Mol. Sci. 2021, 22(19), 10412; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910412 - 27 Sep 2021
Viewed by 300
Abstract
Long-term use of a single fungicide increases the resistance risk and causes adverse effects on natural ecosystems. Controlled release formulations of dual fungicides with different modes of action can afford a new dimension for addressing the current issues. Based on adjustable aperture and [...] Read more.
Long-term use of a single fungicide increases the resistance risk and causes adverse effects on natural ecosystems. Controlled release formulations of dual fungicides with different modes of action can afford a new dimension for addressing the current issues. Based on adjustable aperture and superhigh surface area, metal–organic frameworks (MOFs) are ideal candidates as pesticide release carriers. This study used Al3+ as the metal node and 2-aminoterephthalic acid as the organic chain to prepare aluminum-based metal–organic framework material (NH2-Al-MIL-101) with “cauliflower-like” structure and high surface area of 2359.0 m2/g. Fungicides of azoxystrobin (AZOX) and diniconazole (Dini) were simultaneously encapsulated into NH2-Al-MIL-101 with the loading content of 6.71% and 29.72%, respectively. Dual fungicide delivery system of [email protected]@NH2-Al-MIL-101 demonstrated sustained and pH responsive release profiles. When the maximum cumulative release rate of AZOX and Dini both reached about 90%, the release time was 46 and 136 h, respectively. Furthermore, EC50 values as well as the percentage of inhibition revealed that [email protected]@NH2-Al-MIL-101 had enhanced germicidal efficacy against rice sheath blight (Rhizoctonia solani), evidenced by the synergistic ratio of 1.83. The present study demonstrates a potential application prospect in sustainable plant protection through co-delivery fungicides with MOFs as a platform. Full article
(This article belongs to the Special Issue Synthetic and Natural Antifungals—Desirable and Hazardous Effects)
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Article
Camphor and Eucalyptol—Anticandidal Spectrum, Antivirulence Effect, Efflux Pumps Interference and Cytotoxicity
Int. J. Mol. Sci. 2021, 22(2), 483; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020483 - 06 Jan 2021
Cited by 3 | Viewed by 998
Abstract
Candidaalbicans represents one of the most common fungal pathogens. Due to its increasing incidence and the poor efficacy of available antifungals, finding novel antifungal molecules is of great importance. Camphor and eucalyptol are bioactive terpenoid plant constituents and their antifungal properties have [...] Read more.
Candidaalbicans represents one of the most common fungal pathogens. Due to its increasing incidence and the poor efficacy of available antifungals, finding novel antifungal molecules is of great importance. Camphor and eucalyptol are bioactive terpenoid plant constituents and their antifungal properties have been explored previously. In this study, we examined their ability to inhibit the growth of different Candida species in suspension and biofilm, to block hyphal transition along with their impact on genes encoding for efflux pumps (CDR1 and CDR2), ergosterol biosynthesis (ERG11), and cytotoxicity to primary liver cells. Camphor showed excellent antifungal activity with a minimal inhibitory concentration of 0.125–0.35 mg/mL while eucalyptol was active in the range of 2–23 mg/mL. The results showed camphor’s potential to reduce fungal virulence traits, that is, biofilm establishment and hyphae formation. On the other hand, camphor and eucalyptol treatments upregulated CDR1;CDR2 was positively regulated after eucalyptol application while camphor downregulated it. Neither had an impact on ERG11 expression. The beneficial antifungal activities of camphor were achieved with an amount that was non-toxic to porcine liver cells, making it a promising antifungal compound for future development. The antifungal concentration of eucalyptol caused cytotoxic effects and increased expression of efflux pump genes, which suggests that it is an unsuitable antifungal candidate. Full article
(This article belongs to the Special Issue Synthetic and Natural Antifungals—Desirable and Hazardous Effects)
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