• Title/Summary/Keyword: antifungal drug

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Downregulation of fungal cytochrome c peroxidase expression by antifungal quinonemethide triterpenoids

  • Seo, Woo-Duck;Lee, Dong-Yeol;Park, Ki Hun;Kim, Jin-Hyo
    • 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.

Antifungal and Plant Growth Promotion Activities of Recombinant Defensin Proteins from the Seed of Korean Radish (Raphanus sativus L.)

  • Hwang, Cher-Won
    • Korean Journal of Environmental Agriculture
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    • v.28 no.4
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    • pp.435-441
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    • 2009
  • In the present study, we analyzed the defensin protein deduced from Korean radish (Raphanus sativus L.) seeds.To express the genes in E. coli, we constructed a recombinant expression vector with a defensin gene, named rKRs-AFP gene isolated from Korean radish seeds. Over expressed rKRs-AFP proteins was separated by SDS-PAGE to determine the purity, and protein concentration was determined by the Bradford method. Antifungal activity was assessed by disk assay method against the tested fungi. As a result, when 500 mL of cell culture were disrupted by sonicator, 32.5 mg total proteins were obtained. The purified protein showed a single band on SDS-PAGE with estimated molecular weight about 6 KDa, consistent with the molecular mass calculated from the deduced amino acid sequence. The purified rKRs-AFP protein showed remarkable antifungal activities against several fungi including Aspergillus niger, Botrytis cinerea causing the gray mold disease, and Candida albicans. In field tests using the purified rKRs-AFP protein, the protein showed the reducing activity of disease spot and the mitigating effect of spreading of disease like agrichemicals. The immuno-assay of rKRs-AFP protein showed that the purified protein entirely accumulated at B. cinerea cytoplasm through the hyphal septa shown by fluorescence imaging. There was no fluorescence inside the cell, when the hypha was incubated without the protein. These all results indicate that the recombinant rKRs-AFP proteins can be utilized as a potential antifungal drug to control harmful plant fungal pathogens.

Antifungal Effect of Amentoflavone derived from Selaginella tamariscina

  • Jung, Hyun-Jun;Sung, Woo-Sang;Yeo, Soo-Hwan;Kim, Hyun-Soo;Lee, In-Seon;Woo, Eun-Rhan;Lee, Dong-Gun
    • Archives of Pharmacal Research
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    • v.29 no.9
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    • pp.746-751
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    • 2006
  • Amentoflavone is a plant biflavonoid that was isolated from an ethyl acetate extract of the whole plant of Selaginella tamariscina (Beauv.) spring. 1D and 2D NMR spectroscopy including DEPT, HMQC, and HMBC were used to determine its structure. Amentoflavone exhibited potent antifungal activity against several pathogenic fungal strains but had a very low hemolytic effect on human erythrocytes. In particular, amentoflavone induced the accumulation of intracellular trehalose on C. albicans as a stress response to the drug, and disrupted the dimorphic transition that forms pseudo-hyphae during pathogenesis. In conclusion, amentoflavone has great potential to be a lead compound for the development of antifungal agents.

Antifungal and synergistic effects of an ethyl acetate extract of the edible brown seaweed Eisenia bicyclis against Candida species

  • Kim, Ki-Hyun;Eom, Sung-Hwan;Kim, Hyo-Jung;Lee, Dae-Sung;Nshimiyumukiza, Ossiniel;Kim, Dongsoo;Kim, Young-Mog;Lee, Myung-Suk
    • Fisheries and Aquatic Sciences
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    • v.17 no.2
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    • pp.209-214
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    • 2014
  • With the continuing demand for new solutions in the development of effective and safe candidiasis therapies, we investigated the efficacy of an antifungal agent from the marine brown alga Eisenia bicyclis. The methanolic extract of E. bicyclis evinced potential antifungal activity against Candida species. The ethyl acetate (EtOAc)-soluble extract from E. bicyclis demonstrated the strongest antifungal activity against Candida species among five solvent-soluble extracts. Indeed, the EtOAc-soluble extract showed minimum inhibitory concentrations (MICs) ranging from 4 to 8 mg/mL. Furthermore, the EtOAc-soluble extract considerably reversed high-level fluconazole resistance of Candida species. The MIC values of fluconazole against Candida species decreased substantially (from 64 to $4{\mu}g/mL$) in combination with the MIC of the EtOAc-soluble extract (4 mg/mL). The fractional inhibitory concentration indices of fluconazole ranged from 0.531 to 0.625 in combination with 4, 2, or 1 mg/mL of the EtOAc-soluble extract against Candida isolates, indicating that these combinations exert a marked synergistic effect against Candida isolates. These findings imply that compounds derived from E. bicyclis can be a potential source of natural antifungal agents against Candida species.

Azole Resistance Caused by Increased Drug Efflux in Candida glabrata Isolated from the Urinary Tract of a Dog with Diabetes Mellitus

  • Kim, Minchul;Lee, Hyekyung;Hwang, Sun-Young;Lee, Inhyung;Jung, Won Hee
    • Mycobiology
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    • v.45 no.4
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    • pp.426-429
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    • 2017
  • A yeast-like organism was isolated from a urine sample of a 6-year-old neutered male miniature poodle dog with urinary tract infection, diabetes ketoacidosis, and acute pancreatitis. We identified the yeast-like organism to be Candida glabrata and found that this fungus was highly resistant to azole antifungal drugs. To understand the mechanism of azole resistance in this isolate, the sequences and expression levels of the genes involved in drug resistance were analyzed. The results of our analysis showed that increased drug efflux, mediated by overexpression of ATP transporter genes CDR1 and PDH1, is the main cause of azole resistance of the C. glabrata isolated here.

Control of Aflatoxin and Characteristics of the Quality in Doenjang(soybean paste) Prepared with Antifungal Bacteria (길항미생물에 의한 된장 중 아플라톡신 제어 및 그 품질특성)

  • Kang, Kil-Jin;Park, Jong-Hoon;Cho, Jung-Il
    • Korean Journal of Food Science and Technology
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    • v.32 no.6
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    • pp.1258-1265
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    • 2000
  • In oder to acquire microbial agents that can be utilized for control of aflatoxin produced by Aspergillus. flavus and Asp. parasiticus, antifungal bacteria were isolated. Antifungal bacteria was identified as Bacillus spp. based on morphology and physico-biochemical characteristics. Amount of aflatoxin $B_1$ from Doenjang(soybean paste) prepared with Asp. flavus, Asp. parasiticus, antifungal bacteria(Bacillus sp.), or mixture of Asp. flavus and Asp. parasiticus was 27.2 ppb, 30.3 ppb, 3.4 ppb, and 3.7 ppb, respectively. Aflatoxin $B_1$ was not detected from Doenjang(control) and Doenjang prepared with antifungal bacteria. Content and compositions of free sugars, fatty acid, organic acid and free amino acid in Doenjang prepared with Asp. flavus and Asp. parasiticus, antifungal bacteria and mixture of Asp. flavus and Asp. parasiticus were not significantly different. For volatile flavor compounds of Doenjang prepared with antifungal bacteria, 2-pentyl furan and butanoic acid were disappeared or reduced, while octadecene compounds were produced. However, those of Doenjang prepared with Asp. flavus or Asp. parasiticus and Doenjang(control) were not significantly different. These results suggested that the antifungal bacteria(Bacillus sp.) inhibited production of aflatoxin and that antifungal bacteria did not effect the quality of Doenjang.

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In vivo Anti-fungal Activity of the Essential Oil Fraction from Thymus Species and in vitro Synergism with Clotrimazole

  • Kim, Ji-Hyun;Shin, Seung-Won
    • Natural Product Sciences
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    • v.13 no.3
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    • pp.258-262
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    • 2007
  • The antifungal activity of the essential oil fraction from Thymus magus, and its major component thymol, against Candida albicans was investigated in vitro and in vivo. The combined effects of the oils and clotrimazole, a commonly used antifungal drug for treatment of external candidiasis, were evaluated in this study. In experimental vaginal candidiasis the essential oil fraction of T. magnus resulted in relatively milder inhibition of fungal growth following the inoculation of test mice compared to clotrimazole. However, new fungal growth was not detected up to 12 days after cessation of treatment. In contrast, in a similar experiment using clotrimazole, C. albicans was detected in the $12^{th}$ day post-treatment with the sample. This result indicates that T. magnus oil could be a promising drug to control vaginal candidiasis. In checkerboard titer tests, the combination of clotrimazole with the essential oil fraction of T. magus or T. quinquecostatus resulted in significant synergism, with FIC indices between 0.14 and 0.27 against C. albicans, while clotrimazole combined with thymol, the major component of these oils, produced only an additive effect, with FIC indices ranging between 0.50 and 1.00. Thus, the prominent synergistic effects of clotrimazole combined with T. magus essential oil indicate that these compounds may be an effective treatment for C. albicans infections.

A Nudix Hydrolase Protein, Ysa1, Regulates Oxidative Stress Response and Antifungal Drug Susceptibility in Cryptococcus neoformans

  • Lee, Kyung-Tae;Kwon, Hyojeong;Lee, Dohyun;Bahn, Yong-Sun
    • Mycobiology
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    • v.42 no.1
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    • pp.52-58
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    • 2014
  • A nucleoside diphosphate-linked moiety X (Nudix) hydrolase-like gene, YSA1, has been identified as one of the gromwell plant extract-responsive genes in Cryptococcus neoformans. Ysa1 is known to control intracellular concentrations of ADP-ribose or O-acetyl-ADP-ribose, and has diverse biological functions, including the response to oxidative stress in the ascomycete yeast, Saccharomyces cerevisiae. In this study, we characterized the role of YSA1 in the stress response and adaptation of the basidiomycete yeast, C. neoformans. We constructed three independent deletion mutants for YSA1, and analyzed their mutant phenotypes. We found that ysa1 mutants did not show increased sensitivity to reactive oxygen species-producing oxidative damage agents, such as hydrogen peroxide and menadione, but exhibited increased sensitivity to diamide, which is a thiol-specific oxidant. Ysa1 was dispensable for the response to most environmental stresses, such as genotoxic, osmotic, and endoplasmic reticulum stress. In conclusion, modulation of YSA1 may regulate the cellular response and adaptation of C. neoformans to certain oxidative stresses and contribute to the evolution of antifungal drug resistance.