• Journal of Microbiology and Biotechnology
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• v.17 no.11
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• pp.1797-1804
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• 2007

Lycopene, an acyclic carotenoid found in tomatoes (Lycopersicon esculentum) and a number off fruits, has shown various biological properties, but its antifungal effects remain poorly understood. The current study investigated the antifungal activity of lycopene and its mode of action. Lycopene showed potent antifungal effects toward pathogenic fungi, tested in an energy-independent manner, with low hemolytic effects against human erythrocytes. To confirm the antifungal effects of lycopene, its effects on the dimorphism of Candida albicans induced by fetal bovine serum (FBS), which plays a key role in the pathogenesis of a host invasion, were investigated. The results showed that lycopene exerted potent antifungal activity on the serum-induced mycelia of C. albicans. To understand the antifungal mode of action of lycopene, the action of lycopene against fungal cell membranes was examined by FACScan analysis and glucose and trehalose-release test. The results indicated that lycopene caused significant membrane damage and inhibited the normal budding process, resulting from the destruction of membrane integrity. The present study indicates that lycopene has considerable antifungal activity, deserving further investigation for clinical applications.

• Journal of Microbiology and Biotechnology
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• v.28 no.11
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• pp.1771-1781
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• 2018

The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

• Mycobiology
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• v.47 no.2
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• pp.242-249
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• 2019

Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.

• Genomics & Informatics
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• v.19 no.4
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• pp.39.1-39.8
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• 2021

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)-positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) 'biological process' terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7 breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including 'cell cycle' (cdc2, rik1, pas1, and leo1), 'signaling' (sck2, oga1, and cki3), and 'vesicle-mediated transport' (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the 'signaling' GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

• Microbiology and Biotechnology Letters
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• v.37 no.3
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• pp.273-279
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• 2009

Hyungbangjihwang-Tang (HT), an Oriental herbal formula, has been known to play a role which helps to recover vigor of human in the Orient. In this study, antifungal substance (HTI) was purified from the ethyl-acetate extracts of HT by using $SiO_2$ column chromatography and HPLC, and the antifungal effects of HTI and its mode of action were investigated. By using a broth micro-dilution assay, the activity of HTI was evaluated against fungi. HTI showed antifungal activities without hemolytic effect against human erythrocytes. To confirm antifungal activity of HTI, we examined the accumulation of intracellular trehalose as stress response on toxic agents and effect on dimorphic transition in Candida albicans. The results demonstrated that HTI induced the accumulation of intracellular trehalose and exerted its antifungal effect by disrupting the mycelial forms. To understand its antifungal mode of action, cell cycle analysis was performed with C. albicans, and the results showed HTI arrested the cell cycle at the S phase in yeast. The present study indicates that HTI has considerable antifungal activity, deserving further investigation for clinical applications.

• Korean Journal of Microbiology
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• v.3 no.1
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• pp.15-17
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• 1965

The list of fungi which may be found on leather has already grown to over fifty fungi. Strains of Aspergillus, Penicillium and Paecilomyces appears to be the most common ones. However, there had been no studies concerning the antifungal action of leather in Korea. Therefore the authors attempt to isolate the strains of fungi from leather. In this study, the strains of Aspergillus niger, glaucus and oryzae were isolated respectively out of leather, then it was identified eachly. These strains of fungi could grow in the presence of fat and oils, it is obvious that leather-mildew utilize fat and oils of leather-products as a carbon-saurce.

• Microbiology and Biotechnology Letters
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• v.27 no.5
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• pp.354-358
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• 1999

In order to know the antifungal characteristics of saturated fatty acids having 6 to 12 carbons, their minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) were estimated against Saccharomyces cerevisiae. Fatty acids from C6 to C11 exhibited increasing activity with chain length, but C12 fatty acid did not show activity at all. In relation to antifungal modes of actions, fatty acids investigated showed on inhibitory activity toward the plasma membrane H+-ATPase of Saccharomyces cerevisiae. Their inhibitions to the glucose-induced acidification and ATP hydrolysis caused by the proton pump were found to be in common wiht antifungal activities. At the test concentration of 1mM, hexanoic acid (C6) showed the lowest inhibition of about 30%, while undecanoic acid(C11) showed the strongest inhibition of over 90%. In addition, as seen with antifungal activity, the inhibitory activity of dodecanoic acid (C12) was suddenly reduced to less than 50%.

• Journal of Applied Biological Chemistry
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• v.59 no.4
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• pp.281-284
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• 2016

To handle the development of antifungal drug resistance, the development of new structural modules and new modes of action for antifungals have been highlighted recently. Here, the antifungal activity of quinonemethidal triterpenoids such as celastrol, dihydrocelastrol, iguestein, pristimerin, and tingenone isolated from Tripterygium regelii were identified (MIC $0.269-19.0{\mu}M$). C. glabrata was the most susceptible to quinonemethide among the tested fungi. Furthermore, quinonemethide suppressed cyctochrome c peroxidase expression dramatically, decreasing fungal viability caused by the accumulation of hydrogen peroxide. Thus, cyctochrome c peroxidase downregulation of quinonemethide may be a key mode of action for antifungals.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.1-10
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• 2020

FK506, also known as tacrolimus, is a clinically important immunosuppressant drug and has promising therapeutic potentials owing to its antifungal, neuroprotective, and neuroregenerative activities. To generate various FK506 derivatives, the structure of FK506 has been modified by chemical methods or biosynthetic pathway engineering. Herein, we describe the mode of the antifungal action of FK506 and the structure-activity relationship of FK506 derivatives in the context of immunosuppressive and antifungal activities. In addition, we discuss the neurotrophic mechanism of FK506 known to date, along with the neurotrophic FK506 derivatives with significantly reduced immunosuppressive activity. This review suggests the possibility to generate novel FK506 derivatives as antifungal as well as neuroregenerative/neuroprotective agents.

• Journal of Microbiology and Biotechnology
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• v.18 no.10
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• pp.1729-1734
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• 2008

Chitosan, a cationic polysaccharide, has been widely used as a dietary supplement and in a variety of pharmacological and biomedical applications. The antifungal activity and mechanism of action of low molecular weight water-soluble chitosan (LMWS-chitosan) were studied in fungal cells and vesicles containing various compositions of fungal lipids. LMWS-chitosan showed strong antifungal activity against various pathogenic yeasts and hyphae-forming fungi but no hemolytic activity or cytotoxicity against mammalian cells. The degree of calcein leakage was assessed on the basis of lipid composition (PC/CH; 10:1, w/w). Our result showing that LMWS-chitosan interacts with liposomes demonstrated that chitosan induces leakage from zwitterionic lipid vesicles. Confocal microscopy revealed that LMWS-chitosan was located in the plasma membrane. Finally, scanning electron microscopy revealed that LMWS-chitosan causes significant morphological changes on fungal surfaces. Its potent antibiotic activity suggests that LMWS-chitosan is an excellent candidate as a lead compound for the development of novel anti-infective agents.