Farnesol, a Morphogenetic Autoregulatory Substance in the Dimorphic Fungus Candida albicans, Inhibits Hyphae Growth through Suppression of a Mitogen-Activated Protein Kinase Cascade

Sato, Tatsuki; Watanabe, Toshihiko; Mikami, Takeshi; Matsumoto, Tatsuji

doi:10.1248/bpb.27.751

Cited by 86 publications

(63 citation statements)

References 18 publications

(12 reference statements)

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“…The real role of farnesene derivatives on the growth of promastigote forms of Leishmania is still unclear and needs further studies, although it is pertinent to notice that farnesol, a derivative alcohol from farnesenes, was relevant in increasing susceptibility of the Staphylococcus aureus culture (Kuroda et al, 2007) and against the fungi Candida albicans in culture (Sato et al, 2004). Consequently the action of farnesene derivatives on Leishmania culture, could be related with the enhance of promastigote susceptibility as it was cited in the case of other microorganisms, independent of the evolutionary distance, once there is a drug example with this possible action, which was also cited, the Amphotericin B.…”

Section: Resultsmentioning

confidence: 99%

Essential oil from leaves of Lantana camara: a potential source of medicine against leishmaniasis

Machado

Valente²,

Lesche³

et al. 2012

Rev. bras. farmacogn.

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Abstract:Leishmaniasis is an infection of viscera or tegument caused by protozoa Leishmania sp. The extensive period required for the treatment, which involves the use of toxic medicines, leads patients to drop treatment increasing the development of resistant forms of Leishmania sp. Lantana camara L., Verbenaceae, is a tropical plant native from America. Folk uses have been described for treatment of tumors, tetanus, rheumatism and malaria. This study evaluates the leishmanicidal activity of the essential oil of leaves from L. camara on promastigote forms of Leishmania chagasi and L. amazonensis and its toxic effects on Artemia salina (brine shrimp test), macrophage cultures and BALB/c mice. The chemical composition was evaluated using the gas chromatography coupled with mass spectrometer (GC-MS). Thirty substances, mostly mono and sesquiterpenes were identifi ed. The most representative constituents were: germacrene D (24.90%), farnesene derivatives (22%) and (E)-cariophylene (14.31%). Bioassays revealed a signifi cant leishmanicidal activity of essential oil against L. amazonensis (IC50 0.25 μg/ mL) and a potential toxic effect on Brine shrimp (LC50 10 μg/mL) and macrophage assays (CC50 4 μg/mL), while there was no toxic manifestation on mice. The data show the relevant potential of L. camara as a source of medicine for leishmaniasis treatment.

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Section: Resultsmentioning

confidence: 99%

Essential oil from leaves of Lantana camara: a potential source of medicine against leishmaniasis

Machado

Valente²,

Lesche³

et al. 2012

Rev. bras. farmacogn.

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“…Since growth resumption is a complex process, we cannot determine at this stage whether nutritional and/or cell wall remodeling signals trigger Cek1 activation. Furthermore, quorum sensing could account for it, since tyrosol and farnesol have been recently identified in C. albicans and shown to be involved in morphogenesis (14,32,74) and farnesol has been claimed to decrease mRNAs of HST7 and CPH1. Therefore, upon dilution from stationary phase, relief of quorum-sensingmediated repression could lead to transient activation of the Cek1 kinase (see Fig.…”

Section: Discussionmentioning

confidence: 99%

The Sho1 Adaptor Protein Links Oxidative Stress to Morphogenesis and Cell Wall Biosynthesis in the Fungal Pathogen Candida albicans

Román

Nombela

Pla

2005

Molecular and Cellular Biology

156

236

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The Sho1 adaptor protein is an important element of one of the two upstream branches of the highosmolarity glycerol (HOG) mitogen-activated protein (MAP) kinase pathway in Saccharomyces cerevisiae, a signal transduction cascade involved in adaptation to stress. In the present work, we describe its role in the pathogenic yeast Candida albicans by the construction of mutants altered in this gene. We report here that sho1 mutants are sensitive to oxidative stress but that Sho1 has a minor role in the transmission of the phosphorylation signal to the Hog1 MAP kinase in response to oxidative stress, which mainly occurs through a putative Sln1-Ssk1 branch of the HOG pathway. Genetic analysis revealed that double ssk1 sho1 mutants were still able to grow on high-osmolarity media and activate Hog1 in response to this stress, indicating the existence of alternative inputs of the pathway. We also demonstrate that the Cek1 MAP kinase is constitutively active in hog1 and ssk1 mutants, a phenotypic trait that correlates with their resistance to the cell wall inhibitor Congo red, and that Sho1 is essential for the activation of the Cek1 MAP kinase under different conditions that require active cell growth and/or cell wall remodeling, such as the resumption of growth upon exit from the stationary phase. sho1 mutants are also sensitive to certain cell wall interfering compounds (Congo red, calcofluor white), presenting an altered cell wall structure (as shown by the ability to aggregate), and are defective in morphogenesis on different media, such as SLAD and Spider, that stimulate hyphal growth. These results reveal a role for the Sho1 protein in linking oxidative stress, cell wall biogenesis, and morphogenesis in this important human fungal pathogen.

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“…It is therefore likely that farnesol exerts its effect at early stages of biofilm development. Farnesol inhibits the filamentation pathway in C. albicans (Kruppa et al, 2004;Sato et al, 2004). C. parapsilosis does not generate true hyphae, but it does grow in a pseudohyphal form.…”

Section: Discussionmentioning

confidence: 99%

Phenotype switching affects biofilm formation by Candida parapsilosis

2005

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Generation of biofilms by the pathogenic yeast Candida parapsilosis is correlated closely with disease. The phenomenon of phenotype switching in 20 isolates of C. parapsilosis was examined and the relationship with biofilm development was investigated. Four stable and heritable phenotypes were identified -crepe, concentric, smooth and crater. Cells from crepe and concentric phenotypes are almost entirely pseudohyphal, whilst cells from smooth and crater phenotypes are mostly yeast-like. The pseudohyphae from concentric phenotypes are approximately 45 % wider than those from crepe cells. The cell size of the smooth phenotype is smaller than those of the other three phenotypes. On polystyrene surfaces, the concentric phenotype generates up to twofold more biofilm than the crepe and crater phenotypes. Smooth phenotypes generate the least biofilm. Concentric phenotypes also invade agar surfaces more than the crepe and crater phenotypes, whilst smooth phenotypes do not invade at all. The smooth phenotype, however, grows significantly faster than the others. The quorum-sensing molecule farnesol inhibits formation of biofilms by the crepe, concentric and crater phenotypes. INTRODUCTIONThe yeast Candida parapsilosis is found frequently as a commensal organism on epithelial and mucosal tissues, but it is also an increasing cause of hospital-acquired infection (Weems, 1992). Although C. parapsilosis is responsible for approximately 16 % of general Candida infections, it is a particular problem in critically ill neonates (Hajjeh et al., 2004;Pfaller & Diekema, 2004;Roilides et al., 2004). Fungaemia caused by C. parapsilosis is associated with the presence of catheters and the use of parenteral nutrition (Shin et al., 2002). This is probably due to the ability of the yeast to grow as biofilms, especially in highglucose environments (Branchini et al., 1994). Biofilms are inherently resistant to treatment with antifungal drugs and the infected device must usually be removed.Formation of biofilms by organisms growing in association with a surface is a very common phenomenon among yeast and bacterial species (Hall-Stoodley et al., 2004;Jabra-Rizk et al., 2004). In yeast, the most detailed descriptions of biofilm structure come from studies on Candida albicans (Baillie & Douglas, 1999; Chandra et al., 2001;Hawser & Douglas, 1994;Kumamoto, 2002;Shin et al., 2002). In general, a layer of cells in the yeast form is found attached to the surface, with a layer of filamentous cells above, surrounded by an exopolymeric matrix (Kumamoto, 2002). Cells in biofilms are associated with a specific geneexpression pattern, including the overexpression of amino acid biosynthetic genes, particularly those for amino acids containing sulfur (García-Sánchez et al., 2004). Biofilm growth requires activation of the filamentation pathway and mutants defective in regulators of filamentation, such as efg1 and cph1, are unable to form biofilms (Ramage et al., 2002b). C. parapsilosis is not capable of forming true filaments and biofilms are often composed...

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Farnesol, a Morphogenetic Autoregulatory Substance in the Dimorphic Fungus Candida albicans, Inhibits Hyphae Growth through Suppression of a Mitogen-Activated Protein Kinase Cascade

Cited by 86 publications

References 18 publications

Essential oil from leaves of Lantana camara: a potential source of medicine against leishmaniasis

Essential oil from leaves of Lantana camara: a potential source of medicine against leishmaniasis

The Sho1 Adaptor Protein Links Oxidative Stress to Morphogenesis and Cell Wall Biosynthesis in the Fungal Pathogen Candida albicans

Phenotype switching affects biofilm formation by Candida parapsilosis

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