• Title/Summary/Keyword: hyphal transition

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Deer Antler Extract Selectively Suppresses Hyphal Growth in Dimorphic Fungus, Candida albicans

  • Park, Hyun-Sook;Jeon, Gil-Ja;Choi, Won-Ja
    • Journal of Microbiology and Biotechnology
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    • v.8 no.3
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    • pp.291-294
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    • 1998
  • Transfer of Candida albicans grown in Sabouraud medium to the RPMI medium induces the transition from a nonpathogenic yeast form to a pathogenic hyphal form. This transition was severely inhibited in a dose-dependent manner when deer antler extract was added to the RPMI medium in a nontoxic range (up to $500{\mu}g$). In that range, deer antler extract inhibited the hyphal transition and cell growth, whereas no effect was observed on the yeast growth. When hydrophobic or hydrophilic fractions were prepared by detergent-solubilization of deer antler extract, the hydrophobic fraction showed a large degree of inhibition of the hyphal growth in Candida albicans. Neither fraction affected the growth in the yeast form. The pattern of chitin localization in the culture of the yeast form grown in RPMI in the presence of deer antler extract was confirmed by calcofluor staining and this exhibited strongly the suppression of hyphal transition.

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Hyphal Growth Inhibition by Deer Antler Extract Mimics the Effect of Chitin Synthase Deletion in Candida albicans

  • Park, Hyun-Sook;Jhon, Gil-Ja;Choi, Won-Ja
    • Journal of Microbiology and Biotechnology
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    • v.8 no.4
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    • pp.422-425
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    • 1998
  • Chitin synthase null-mutants propagate in yeast form in RPMI medium with suppression of hyphal growth. This hyphal suppression is also observed in the wild type culture grown in RPMI medium supplemented with deer antler extract. To identify the possible target of deer antler extract, the enzymatic activities of chitin synthases were examined. The enzymatic activities of three chitin synthases, CAChsl, CAChs2, and CAChs3, were found to be differentially inhibited by deer antler extract. Of them, CAChsl, was the most sensitive to the extract. These results indicate that deer antler extract causes hyphal suppression, which resembles the effects of chitin synthase deletion, probably through direct inhibition of chitin synthases.

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Lysophosphatidylcholine Suppresses the Expression of Phr1p and Pra1p, Surface Proteins Involved in the Morphogenesis of Candida albicans

  • Shin, Duck-Hyang;Choi, Won-Young;Yoo, Yung-Joon;Kim, Min-Kyoung;Choi, Won-Ja
    • Journal of Microbiology and Biotechnology
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    • v.14 no.4
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    • pp.868-871
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    • 2004
  • Candida albicans has become the most important human pathogen in immunocompromised patients. One important feature of the pathogenicity in C. albicans is the morphological transition from yeast to hyphae. Previously, we reported that lysophosphatidylcholine (Lyso-PC) suppressed the hyphal transition through the MAP kinase pathway (Min et al., 2001). Therefore, it should be useful to examine the unknown genes involved in the MAP kinase pathway. As a way to identify target genes of Lyso-PC in hyphal suppression, this present study exploited two-dimensional electrophoresis. It was revealed that Lyso-PC suppressed expression of Phr1p and Pra1p, surface proteins involved in the morphogenesis.

Resveratrol Impaired the Morphological Transition of Candida albicans Under Various Hyphae-Inducing Conditions

  • Okamoto-Shibayama, Kazuko;Sato, Yutaka;Azuma, Toshifumi
    • Journal of Microbiology and Biotechnology
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    • v.20 no.5
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    • pp.942-945
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    • 2010
  • The ability of the human fungal pathogen Candida albicans to undergo the morphological transition from a single yeast form to pseudohyphal and hyphal forms in response to various conditions is known to be important for its virulence. Many studies have shown the pharmacological effects of resveratrol, a phytoalexin polyphenolic compound. In this study, we investigated the antifungal activity of resveratrol against C. albicans. Both yeast-form and mycelial growth of C. albicans were inhibited by resveratrol. In addition, normal filamentation of C. albicans was affected and yeast-to-hypha transition under serum-, pH-, and nutrient-induced hyphal growth conditions was impaired by resveratrol.

Immunological Features of Macrophages Induced by Various Morphological Structures of Candida albicans

  • Han, Kyoung-Hee;Park, Su Jung;Choi, Sun Ju;Park, Joo Young;Lee, Kyoung-Ho
    • Journal of Microbiology and Biotechnology
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    • v.23 no.7
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    • pp.1031-1040
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    • 2013
  • Candida albicans is a dimorphic fungus that commensally colonizes human mucosal surfaces. The aim of this study was to assess the role of different C. albicans morphologies in inducing pattern recognition receptors (PRRs) and cytokines in macrophages. Macrophages may respond to pathogen-associated molecular patterns via TLR2 and TLR4 by expressing cytokines. The hyphal transition of C. albicans was induced by 20% serum (S), RPMI-1640 (R), or $39^{\circ}C$ culture (H). Macrophages were then challenged with either yeast (Y) or different hyphae cultures of C. albicans, followed by RT-PCR and FACS analysis of PRRs expression. In addition, macrophages were stimulated with either yeast or different hyphae cultures of C. albicans used by RT-PCR and Bio-Plex analysis of cytokines production. Macrophages expressed high levels of TLR4 and dectin-1 after stimulation with Y cells. In contrast, stimulation with H or R cells strongly increased the expression of TLR2 and dectin-2. Stimulation with Y cells significantly enhanced the expression of IL-$1{\beta}$ and weakly increased the expression of IL-6 and IL-12. Stimulation with hyphal cells (S, R, and H) strongly increased IL-10 expression, but weakly reduced IL-$1{\beta}$ expression. The phagocytosis activity and NO production of macrophages were decreased upon treatment with hyphal cells compared with yeast, and depended on the length of hyphae. In summary, the yeast and hyphae forms of C. albicans resulted in an induction of different PRRs, with accompanying differences in immune cell cytokine profiles.

Disruption of the Dual Specificity Kinase Gene Causes the Reduction of Virulence in Candida albicans (이중특이성 인산화 효소의 결손이 Candida albicans 병원성에 미치는 효과)

  • Park, Yun-Hee;Park, Hee-Moon
    • The Korean Journal of Mycology
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    • v.39 no.1
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    • pp.85-87
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    • 2011
  • The opportunistic human pathogen Candida albicans has the ability to convert from yeast-form to pseudohyphal or true hyphal form. The morphological transition is considered as an important virulence factor, because the decrease or lack in dimorphism causes the reduction of virulence. Our previous study revealed that the disruption of dual specificity kinase gene caused the reduction of dimorphism in C. albicans. Therefore we tested the effect of dual specificity kinase in virulence using mouse model. The mean survival time for kinase-defective strains was about 15 days in comparison with those of wild-type, 3.9 days. Moreover the fungal burden on kidneys for kinase-defective strains was decreased by ten-fold than that for wild-type. These results suggest possible involvement of dual specificity kinase in a novel signal transduction pathway for morphological transition and virulence of C. albicans.

Characterization of Osh3, an Oxysterol-binding Protein, in Filamentous Growth of Saccharomyces cerevisiae and Candida albicans

  • Hur, Hyang-Sook;Ryu, Ji-Ho;Kim, Kwang-Hoon;Kim, Jin-Mi
    • Journal of Microbiology
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    • v.44 no.5
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    • pp.523-529
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    • 2006
  • OSH3 is one of the seven yeast homologues of the oxysterol binding proteins (OSBPs) which have the major binding affinity to the oxysterols and function as regulator of cholesterol biosynthesis in mammals. Mutational analysis of OSH3 showed that OSH3 plays a regulatory role in the yeast-to-hyphal transition through its oxysterol-binding domain in Saccharomyces cerevisiae. The OSH3 gene was also identified in the pathogenic yeast Candida albicans. Deletion of OSH3 caused a defect in the filamentous growth, which is the major cause of the C. albicans pathogencity. The filamentation defect of the mutation in the MAPK-associated transcription factor, namely $cph1{\Delta}$ was suppressed by overexpression of OSH3. These findings suggest the regulatory roles of OSH3 in the yeast filamentous growth and the functional conservations of OSH3 in S. cerevisiae and C. albicans.

Mode of Action of Coptidis Rhizoma Protein (CRP) and Its Activity Against Subcutaneous Candidiasis due to Candida albicans (황련단백질의 항캔디다 작용기전 및 항피부캔디다증 효과)

  • Lee, Jue-Hee;Shim, Jin Kie;Han, Yongmoon
    • YAKHAK HOEJI
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    • v.49 no.5
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    • pp.422-427
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    • 2005
  • Our previous data showed the protein isolated from Coptidis Rhizoma (CRP) had antifungal activity. In present study, we examined mode of action of the CRP and its activity against subcutaneous candidiasis due to C. albicans yeast cells. Results showed that the CRP blocked hyphal production from yeast form of C. albicans. The CRP also activated RAW 264.7 monocyte/macrophage cell line, which resulted in nitiric oxide (NO) production from the cells. This activation seemed to increase macrophage phagocytosis to destroy the invaders. Like other antimicrobial peptides, CRP was influenced by ionic strength, thus resulting in a decrease of antifungal activity. In murine model of a subcutaneous candidiasis, the sizes of infected areas of the nude mice given the CRP after subcutaneous injection of C. albicans yeast cells to the dorsal skin were $90\%$ less than those of the nude mice groups that received DPBS instead of the CRP. All data indicate that the CRP, which appeared to act like an antimicrobial peptide and to inhibit the morphological transition from blastoconidia, was effec­tive against the subcutaneous disease.

Roles of Zinc-responsive Transcription Factor Csr1 in Filamentous Growth of the Pathogenic Yeast Candida albicans

  • Kim, Min-Jeong;Kil, Min-Kwang;Jung, Jong-Hwan;Kim, Jin-Mi
    • Journal of Microbiology and Biotechnology
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    • v.18 no.2
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    • pp.242-247
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    • 2008
  • In the fungal pathogen Candida albicans, the yeast-to-hyphal transition occurs in response to a broad range of environmental stimuli and is considered to be a major virulence factor. To address whether the zinc homeostasis affects the growth or pathogenicity of C. albicans, we functionally characterized the zinc-finger protein Csr1 during filamentation. The deduced amino acid sequence of Csr1 showed a 49% similarity to the zinc-specific transcription factor, Zap1 of Saccharomyces cerevisiae. Sequential disruptions of CSR1 were carried out in diploid C. albicans. The csr1/csr1 mutant strain showed severe growth defects under zinc-limited growth conditions and the filamentation defect under hypha-inducing media. The colony morphology and the germ-tube formation were significantly affected by the csr1 mutation. The expression of the hyphae-specific gene HWP1 was also impaired in csr1/csr1 cells. The C. albicans homologs of ZRTl and ZRT2, which are zinc-transporter genes in S. cerevisiae, were isolated. High-copy number plasmids of these genes suppressed the filamentation defect of the csr1/csr1 mutant strain. We propose that the filamentation phenotype of C. albicans is closely associated with the zinc homeostasis in the cells and that Csr1 plays a critical role in this regulation.

Relative Risk of Virulence Factors in Candida-Infected Mouse (캔디다균 감염 마우스 모델에서 병독인자의 비교위험도)

  • Kim, Dong-Hwa;Shin, Woon-Seob;Lee, Kyoung-Ho;Kim, Kyung-Hoon;Park, Yoon-Sun;Park, Joo-Young;Koh, Choon-Myung
    • The Journal of the Korean Society for Microbiology
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    • v.35 no.4
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    • pp.317-324
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    • 2000
  • Candida albicans is one of the most frequently isolated fungal pathogens in human. Recently, the prevalence of candida infection has markedly increased, partially due to the increase of immunocompromised hosts. Proposed virulence factors of the pathogenic Candida are the ability to form hyphae to adhere to epithelial cell surfaces, and to secrete acid proteinases and phospholipases. We measured the relative cell surface hydrophobicity (CSH) and the ability of proteinase production (PROT), phospholipase production (PLase), adherence to host epithelium (ADH), and hyphal transition (Germ). The relative risk of virulence factors was analyzed by lethality test in murine model of hematogeneously disseminated candidal infection. According to Cox's proportional hazard analysis, the statistically significant virulence factors were PROT, ADH, and CSH. PROT was the highest risk factor of them. To evaluate the applicability for the diagnosis and treatment of Candidiasis, we examined the protective effect of the active and passive immunizations with the materials purified from virulence factors and antibodies to them in Candia-infected mice model. The mean survival times of active and passive immunized groups were slightly longer than those of non-immunized groups.

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