Tight Control of Trehalose Content Is Required for Efficient Heat-induced Cell Elongation in Candida albicans

Serneels, Joke; Tournu, Hélène; Dijck, Patrick Van

doi:10.1074/jbc.m112.402651

Cited by 24 publications

(20 citation statements)

References 51 publications

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“…This disaccharide is considered not only a storage carbohydrate and stress-protectant, but it also acts as regulator of many cellular processes (Thevelein and Hohmann 1995;Singer and Lindquist 1998;Franç ois and Parrou 2001), and is considered an important target for fungal chemotherapy (Zaragoza et al 1998(Zaragoza et al , 2002Van Dijck et al 2002;Petzold et al 2006;Kingsbury et al 2006;Pedreno et al 2007;Serneels et al 2012;Tournu et al 2013;Sánchez-Fresneda et al, 2014). In the yeast Saccharomyces cerevisiae two distinct pathways for trehalose assimilation can be found.…”

Section: Introductionmentioning

confidence: 99%

Secretion of the acid trehalase encoded by the CgATH1 gene allows trehalose fermentation by Candida glabrata

Zilli

Lopes

Alves

et al. 2015

Microbiological Research

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The emergent pathogen Candida glabrata differs from other yeasts because it assimilates only two sugars, glucose and the disaccharide trehalose. Since rapid identification tests are based on the ability of this yeast to rapidly hydrolyze trehalose, in this work a biochemical and molecular characterization of trehalose catabolism by this yeast was performed. Our results show that C. glabrata consumes and ferments trehalose, with parameters similar to those observed during glucose fermentation. The presence of glucose in the medium during exponential growth on trehalose revealed extracellular hydrolysis of the sugar by a cell surface acid trehalase with a pH optimum of 4.4. Approximately ∼30% of the total enzymatic activity is secreted into the medium during growth on trehalose or glycerol. The secreted enzyme shows an apparent molecular mass of 275 kDa in its native form, but denaturant gel electrophoresis revealed a protein with ∼130 kDa, which due to its migration pattern and strong binding to concanavalin A, indicates that it is probably a dimeric glycoprotein. The secreted acid trehalase shows high affinity and activity for trehalose, with Km and Vmax values of 3.4 mM and 80 U (mg protein)(-1), respectively. Cloning of the CgATH1 gene (CAGLOK05137g) from de C. glabrata genome, a gene showing high homology to fungal acid trehalases, allowed trehalose fermentation after heterologous expression in Saccharomyces cerevisiae.

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Section: Introductionmentioning

confidence: 99%

Secretion of the acid trehalase encoded by the CgATH1 gene allows trehalose fermentation by Candida glabrata

Zilli

Lopes

Alves

et al. 2015

Microbiological Research

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“…We are currently identifying other Upc2-regulated genes by performing chromatin immunoprecipitation-sequencing (ChIP-seq) and RNA-seq analyses. We cannot exclude a possible connection with the previously established pathways in the Hsp90-dependent morphogenetic circuitry, such as the cAMP-PKA and cell cycle pathways or the Pho85-Pcl1-Hms1 module (13,14,46,65,69) or a novel, yet-tobe-determined pathway. Ascorbic acid or Upc2 may be required for the modulation of an inhibitor of these Hsp90 signaling modules.…”

Section: Discussionmentioning

confidence: 95%

Ascorbic Acid Inhibition of Candida albicans Hsp90-Mediated Morphogenesis Occurs via the Transcriptional Regulator Upc2

2014

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Morphogenetic transitions of the opportunistic fungal pathogen Candida albicans are influenced by temperature changes, with induction of filamentation upon a shift from 30 to 37°C. Hsp90 was identified as a major repressor of an elongated cell morphology at low temperatures, as treatment with specific inhibitors of Hsp90 results in elongated growth forms at 30°C. Elongated growth resulting from a compromised Hsp90 is considered neither hyphal nor pseudohyphal growth. It has been reported that ascorbic acid (vitamin C) interferes with the yeast-to-hypha transition in C. albicans. In the present study, we show that ascorbic acid also antagonizes the morphogenetic change caused by hampered Hsp90 function. Further analysis revealed that Upc2, a transcriptional regulator of genes involved in ergosterol biosynthesis, and Erg11, the target of azole antifungals, whose expression is in turn regulated by Upc2, are required for this antagonism. Ergosterol levels correlate with elongated growth and are reduced in cells treated with the Hsp90 inhibitor geldanamycin (GdA) and restored by cotreatment with ascorbic acid. In addition, we show that Upc2 appears to be required for ascorbic acid-mediated inhibition of the antifungal activity of fluconazole. These results identify Upc2 as a major regulator of ascorbic acid-induced effects in C. albicans and suggest an association between ergosterol content and elongated growth upon Hsp90 compromise.

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“…Validamycin A (35), the most active compound of the complex, is a fungicide that inhibits trehalases, enzymes that carry out the degradation of the nonreducing disaccharide trehalose [368][369][370] in plants, insects, and fungi as well as enhancing trehalose accumulation in transgenic plants. It is widely used in rice-producing countries in Asia to control sheath blight disease of the rice plants caused by the fungus Rhizoctonia solani [371][372][373][374][375][376][377][378][379][380][381][382][383][384][385].…”

Section: International Journal Of Carbohydrate Chemistrymentioning

confidence: 99%

Biosynthesis and Biological Activity of Carbasugars

Roscales

Plumet

2016

International Journal of Carbohydrate Chemistry

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The first synthesis of carbasugars, compounds in which the ring oxygen of a monosaccharide had been replaced by a methylene moiety, was described in 1966 by Professor G. E. McCasland's group. Seven years later, the first true natural carbasugar (5a-carba-R-D-galactopyranose) was isolated from a fermentation broth of Streptomyces sp. MA-4145. In the following decades, the chemistry and biology of carbasugars have been extensively studied. Most of these compounds show interesting biological properties, especially enzymatic inhibitory activities, and, in consequence, an important number of analogues have also been prepared in the search for improved biological activities. The aim of this review is to give coverage on the progress made in two important aspects of these compounds: the elucidation of their biosynthesis and the consideration of their biological properties, including the extensively studied carbapyranoses as well as the much less studied carbafuranoses.

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Tight Control of Trehalose Content Is Required for Efficient Heat-induced Cell Elongation in Candida albicans

Cited by 24 publications

References 51 publications

Secretion of the acid trehalase encoded by the CgATH1 gene allows trehalose fermentation by Candida glabrata

Secretion of the acid trehalase encoded by the CgATH1 gene allows trehalose fermentation by Candida glabrata

Ascorbic Acid Inhibition of Candida albicans Hsp90-Mediated Morphogenesis Occurs via the Transcriptional Regulator Upc2

Biosynthesis and Biological Activity of Carbasugars

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