• Title/Summary/Keyword: antifungal mechanism

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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.

Translation Inhibition Activity and Antifungal Activity of Korean Propolis (프로폴리스의 단백질합성저해활성 및 항진균활성)

  • Goh, Ah-Ra;Choi, Kap-Seong;Choi, Sang-Ki
    • Microbiology and Biotechnology Letters
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    • v.38 no.1
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    • pp.64-69
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    • 2010
  • It has been known that propolis possesses anti-infective, anti-inflammatory, and anti-oxidative properties. Although antifungal activity of Propolis has already been demonstrated, very few studies has been conducted for action mechanism and its spectrum on fungi. We found that ethanol extract of propolis (EEP) inhibited in vitro translation. Since we also observed the growth inhibition of pathogenic fungi and anti-oxidative properties preliminarily, we try to see where those properties come from. Therefore we extracted the EEP further with chloroform, ethyl acetate and butanol. When their fractions were examined for the growth inhibition of Candida albicans, Saccharomyces cerevisiae, Candida glabrata, Candida lusitaniae, Cryptococcos neoformans, chloroform fraction exhibited the highest anti-fungal as well as anti-oxidative properties. Similarly the chloroform fraction showed highest translation-inhibiting activities among the various Propolis fractions. These data indicate that those properties might come from similar compounds.

Diversity and Active Mechanism of Fengycin-Type Cyclopeptides from Bacillus subtilis XF-1 Against Plasmodiophora brassicae

  • Li, Xing-Yu;Mao, Zi-Chao;Wang, Yue-Hu;Wu, Yi-Xing;He, Yue-Qiu;Long, Chun-Lin
    • Journal of Microbiology and Biotechnology
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    • v.23 no.3
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    • pp.313-321
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    • 2013
  • Bacillus subtilis XF-1, a strain with demonstrated ability to control clubroot disease caused by Plasmodiophora brassicae, was studied to elucidate its mechanism of antifungal activity against P. brassicae. Fengycin-type cyclopeptides (FTCPs), a well-known class of compounds with strong fungitoxic activity, were purified by acid precipitation, methanol extraction, and chromatographic separation. Eight homologs of fengycin, seven homologs of dehydroxyfengycin, and six unknown FTCPs were characterized with LC/ESI-MS, LC/ESI-MS/MS, and NMR. FTCPs (250 ${\mu}g/ml$) were used to treat the resting spores of P. brassicae ($10^7/ml$) by detecting leakage of the cytoplasm components and cell destruction. After 12 h treatment, the absorbencies at 260 nm ($A_{260}$) and at 280 nm ($A_{280}$) increased gradually to approaching the maximum of absorbance, accompanying the collapse of P. brassicae resting spores, and nearly no complete cells were observed at 24 h treatment. The results suggested that the cells could be cleaved by the FTCPs of B. subtilis XF-1, and the diversity of FTCPs was mainly attributed to a mechanism of clubroot disease biocontrol.

trans-Cinnamaldehyde-Induced Apoptosis in AGS Cells (AGS 세포주에서 트랜스 신남알데하이드의 세포 사멸 유도)

  • Lee, Sunyi;Jung, Joohee
    • Journal of Food Hygiene and Safety
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    • v.36 no.1
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    • pp.100-104
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    • 2021
  • trans-Cinnamaldehyde (TCA), as one of the active ingredients in cinnamon, has been reported to have antiviral, antibacterial and antifungal effects as well as anti-cancer effects in several cancer cell lines. However, reports of TCA in gastric cancer are rare, and its mechanism is unclear. In this study, we investigated the anti-proliferative effect of TCA and its mechanism in gastric cancer AGS cells. TCA dose-dependently inhibited the cell viability of AGS cells. Our results suggested that TCA induces apoptosis through changes in cell morphology. To elucidate its mechanism, we investigated the expression level of apoptosis-related proteins. TCA induced the expression of p53 and Bax proteins, and then increased the cleaved caspase 9 and cleaved PARP. These results indicated that TCA triggers apoptosis via p53 pathway in AGS cells. Our results suggested that TCA might be a new anticancer drug candidate for gastric cancer.

Biphasic augmentation of alpha-adrenergic contraction by plumbagin in rat systemic arteries

  • Kim, Hae Jin;Yoo, Hae Young;Zhang, Yin Hua;Kim, Woo Kyung;Kim, Sung Joon
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.6
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    • pp.687-694
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    • 2017
  • Plumbagin, a hydroxy 1,4-naphthoquinone compound from plant metabolites, exhibits anticancer, antibacterial, and antifungal activities via modulating various signaling molecules. However, its effects on vascular functions are rarely studied except in pulmonary and coronary arteries where NADPH oxidase (NOX) inhibition was suggested as a mechanism. Here we investigate the effects of plumbagin on the contractility of skeletal artery (deep femoral artery, DFA), mesenteric artery (MA) and renal artery (RA) in rats. Although plumbagin alone had no effect on the isometric tone of DFA, $1{\mu}M$ phenylephrine (PhE)-induced partial contraction was largely augmented by plumbagin (${\Delta}T_{Plum}$, 125% of 80 mM KCl-induced contraction at $1{\mu}M$). With relatively higher concentrations (>$5{\mu}M$), plumbagin induced a transient contraction followed by tonic relaxation of DFA. Similar biphasic augmentation of the PhE-induced contraction was observed in MA and RA. VAS2870 and GKT137831, specific NOX4 inhibitors, neither mimicked nor inhibited ${\Delta}T_{Plum}$ in DFA. Also, pretreatment with tiron or catalase did not affect ${\Delta}T_{Plum}$ of DFA. Under the inhibition of PhE-contraction with L-type $Ca^{2+}$ channel blocker (nifedipine, $1{\mu}M$), plumbagin still induced tonic contraction, suggesting $Ca^{2+}$-sensitization mechanism of smooth muscle. Although ${\Delta}T_{Plum}$ was consistently observed under pretreatment with Rho A-kinase inhibitor (Y27632, $1{\mu}M$), a PKC inhibitor (GF 109203X, $10{\mu}M$) largely suppressed ${\Delta}T_{Plum}$. Taken together, it is suggested that plumbagin facilitates the PKC activation in the presence of vasoactive agonists in skeletal arteries. The biphasic contractile effects on the systemic arteries should be considered in the pharmacological studies of plumbagin and 1,4-naphthoquinones.

Excited State Dynamics of Curcumin and Solvent Hydrogen Bonding

  • Yang, Il-Seung;Jin, Seung-Min;Kang, Jun-Hee;Ramanathan, Venkatnarayan;Kim, Hyung-Min;Suh, Yung-Doug;Kim, Seong-Keun
    • Bulletin of the Korean Chemical Society
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    • v.32 no.spc8
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    • pp.3090-3093
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    • 2011
  • Curcumin is a natural product with antioxidant, anti-inflammatory, antiviral and antifungal functions. As it is known that the excited state intramolecular hydrogen transfer of curcumin are related to its medicinal antioxidant mechanism, we investigated its excited state dynamics by using femtosecond transient absorption spectroscopy in an effort to understand the molecule's therapeutic effect in terms of its photophysics and photochemistry. We found that stronger intermolecular hydrogen bonding with solvents weakens the intramolecular hydrogen bonding and decelerates the dynamical process of the enolic hydrogen. Exceptions are found in methanol and ethylene glycol due to their nature as simultaneous hydrogen bonding donor-acceptor and high viscosity solvent, respectively.

Cloning and mutational analysis of pyrroquinoline quinone(PQQ) genes from a phosphate - solubilizing biocontrol bacterium Enterobacter intermedium.

  • Han, Song-Hee;Cho, Baik-Ho;Kim, Young-Cheol
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.94.2-95
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    • 2003
  • E. intermedium 60-2G possessing a strong ability to solubilize insoluble phosphate, has plant growth-promoting activity, induced systemic resistance activity against scab pathogen in cucumber, and antifungal activity against various phytopathogenic fungi. The phosphate solubilizing activity of 60-2G may be mainly accomplished by production of gluconic acid through a direct extracellular oxidation of glucose by glucose dehydrogenase that required a PQQ cofactor for its activation. A pqq gene cluster conferred Phosphate-solubilizing activity in E. coli DH5${\alpha}$ was cloned and sequenced. The 6,783 bP pqq sequence had six open reading frames (from A to F) and showed 50-95% homology to pqq genes from other bacteria. The E. coli strain expressing the pqq genes solubilized phosphate from hydroxyapatite after a pH drop to 4.0, which paralleled in time the secretion of gluconic acid. To study the role of PQQ in biocontrol traits of E. intermedium, PQQ mutants of 60-2G were constructed by marker exchangee mutagenesis. The PQQ mutants of E. intermedium were lost activities of solubilizing phosphate, growth inhibition of phytopathogenic fungi, and plant growth promotion. These findings suggest that PQQ plays an important role, possibly activation of certain enzymes, in several beneficial bacterial traits of E. intermedium by as yet an unknown mechanism.

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The Microsponge Delivery System of Itraconazole: Preparation, Characterization and Release Studies (이트라코나졸 마이크로스폰지의 약물 전달 시스템: 제조, 특성 및 방출 연구)

  • Cho, Young-Ho;Lee, Jong-Hwa;Kim, Hak-Hyung;Lee, Gye-Won
    • KSBB Journal
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    • v.26 no.3
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    • pp.217-222
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    • 2011
  • Itraconazole is a triazole antifungal agent to inhibit most fungal pathogens. To improve the oral absorption and dissolution of poorly water-soluble itraconazole, microsponge system composed of $Eudragit^{(R)}$ E100 and polyvinyl alcohol(PVA) formulated by quasi-emulsion solvent diffusion method, and its physicochemical properties and pharmacokinetic parameters of itraconazole were studied. The microsponge of itraconazole were discrete free flowing micro sized particles with perforated orange peel like morphology as visualized by scanning electron microscope (SEM). Results showed that the drug loading efficiency, production yield, and particle size of itraconazole microsponge were affected by drug to polymer ratio, the volume of internal phase containing methylene chloride, stirring rate and the concentration of PVA used. Also, the results showed that the dissolution rate of itraconazole from the microsponges was affected by drug to polymer ratio. In other words, the release rate of itraconazole from microsponges was increased from at least 27.43% to 64.72% after 2 h. The kinetics of dissolution mechanism showed that the dissolution data followed Korsmeyer-Peppas model. Therefore, these results suggest that microsponge system can be useful for the oral delivery of itraconazole by manipulating the release profile.

Identification of Differentially Expressed Genes (DEGs) by Malachite Green in HepG2 Cells

  • Kim, Youn-Jung;Song, Mee;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.4 no.1
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    • pp.22-30
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    • 2008
  • Malachite Green (MG), a toxic chemical used as a dye, topical antiseptic and antifungal agent for fish, is highly soluble in water, cytotoxic to various mammalian cells and also acts as a liver tumor promoter. In view of its industrial importance and possible exposure to human beings, MG possesses a potential environmental health hazard. So, we performed with HepG2, a human hepatocellular carcinoma cell line, to identify the differentially expressed genes (DEGs) related to toxicity of MG. And we compared gene expression between control and MG treatment to identify genes that are specifically or predominantly expressed by employing annealing control primer (ACP)-based $GeneFishing^{TM}$ method. The cytotoxicity $(IC_{20})$ of MG was determined above the $0.867{\mu}M$ in HepG2 cell for 48 h treatment. And the DEGs of MG were identified that 5 out of 6 DEGs were upregulated and 1 out of 6 DEGs was down-regulated by MG. Also, MG induced late apoptosis and necrosis in a dose dependent in flow cytometric analysis. Through further investigation, we will identify more meaningful and useful DEGs on MG, and then can get the information on mechanism and pathway associated with toxicity of MG.

Exogenous Indole Regulates Lipopeptide Biosynthesis in Antarctic Bacillus amyloliquefaciens Pc3

  • Ding, Lianshuai;Zhang, Song;Guo, Wenbin;Chen, Xinhua
    • Journal of Microbiology and Biotechnology
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    • v.28 no.5
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    • pp.784-795
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    • 2018
  • Bacillus amyloliquefaciens Pc3 was isolated from Antarctic seawater with antifungal activity. In order to investigate the metabolic regulation mechanism in the biosynthesis of lipopeptides in B. amyloliquefaciens Pc3, GC/MS-based metabolomics was used when exogenous indole was added. The intracellular metabolite profiles showed decreased asparagine, aspartic acid, glutamine, glutamic acid, threonine, valine, isoleucine, hexadecanoic acid, and octadecanoic acid in the indole-treated groups, which were involved in the biosynthesis of lipopeptides. B. amyloliquefaciens Pc3 exhibited a growth promotion, bacterial total protein increase, and lipopeptide biosynthesis inhibition upon the addition of indole. Besides this, real-time PCR analysis further revealed that the transcription of lipopeptide biosynthesis genes ituD, fenA, and srfA-A were downregulated by indole with 22.4-, 21.98-, and 26.0-fold, respectively. It therefore was speculated that as the metabolic flux of most of the amino acids and fatty acids were transferred to the synthesis of proteins and biomass, lipopeptide biosynthesis was weakened owing to the lack of precursor amino acids and fatty acids.