Fungal heat-shock proteins in human disease

Burnie, James; Carter, Tracey L.; Hodgetts, Samantha; Matthews, Ruth

doi:10.1111/j.1574-6976.2005.00001.x

Cited by 135 publications

(114 citation statements)

References 445 publications

(479 reference statements)

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“…It is known that microorganisms including T. rubrum 18 acquire thermotolerance by producing heat shock proteins with various roles such as chaperone activity, ribosomal stability, etc. However, the heat-stressed hyphae of T. mentagrophytes in our study were killed with little structural alteration.…”

Section: Discussionmentioning

confidence: 99%

Combined Effect of Heat, Essential Oils and Salt on the Fungicidal Activity against Trichophyton mentagrophytes in Foot Bath

Inouye

Uchida²,

Nishiyama

et al. 2007

Nippon Ishinkin Gakkai Zasshi

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This work was originally undertaken to determine the effective conditions of essential oils against Trichophyton mentagrophytes in vitro for the treatment of tinea pedis in a foot bath. Agar blocks implanted with T. mentagrophytes were immersed in 0.1% aqueous agar containing two-fold dilutions of essential oils with or without sodium chloride at 27 C, 37 C and 42 C for 10 and 20 min. The number of surviving mycelia on the agar blocks was determined from the standard curves of the colony diameter and original inocula of the conidia. At the same time, the thermal effect on the cellular morphology was examined using SEM. Most fungal mycelia 99.7% were killed after treatment at 42 C for 20 min without essential oil. The fungicidal activity of essential oils was markedly enhanced by treating at 42 C for 20 min as compared with that at 27 C, showing 1/4 1/32-fold reduction of minimum fungicidal concentration MFC to kill 99.99% . The order of the fungicidal activity of 11 essential oils was oregano, thyme thymol, cinnamon bark lemongrass clove, palmarose, peppermint, lavender geranium Bourbon, tea tree thyme geraniol oils. MFCs were further reduced to 1/2 1/8 by the addition of 10% sodium chloride. The salt effect was explained, at least partly, by an increase in mycelial adsorption of antifungal constituents in the presence of sodium chloride. Considerable hyphal damage was done at 27 C by the essential oils, but no further alteration in morphology of the hyphae treated at 42 C with or without oil was observed by SEM. The inhibitory effect of heat and oils was also observed against mycelia of T. rubrum and conidia of T. mentagrophytes. Thermotherapy combined with essential oils and salt would be promising to treat tinea pedis in a foot bath.

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Section: Discussionmentioning

confidence: 99%

Combined Effect of Heat, Essential Oils and Salt on the Fungicidal Activity against Trichophyton mentagrophytes in Foot Bath

Inouye

Uchida²,

Nishiyama

et al. 2007

Nippon Ishinkin Gakkai Zasshi

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“…Seven other HSP70 sequences were detected in our EST collection. Heat shock proteins may not only be involved in environmental adaptation processes but are also known to be immunodominant antigens, e.g., in the related dermatophyte T. mentagrophytes and other fungal pathogens (1,22).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling in the Human Pathogenic Dermatophyte Trichophyton rubrum during Growth on Proteins

et al. 2009

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Dermatophytes are highly specialized filamentous fungi which cause the majority of superficial mycoses in humans and animals. The high secreted proteolytic activity of these microorganisms during growth on proteins is assumed to be linked to their particular ability to exclusively infect keratinized host structures such as the skin stratum corneum, hair, and nails. Individual secreted dermatophyte proteases were recently described and linked with the in vitro digestion of keratin. However, the overall adaptation and transcriptional response of dermatophytes during protein degradation are largely unknown. To address this question, we constructed a cDNA microarray for the human pathogenic dermatophyte Trichophyton rubrum that was based on transcripts of the fungus grown on proteins. Profiles of gene expression during the growth of T. rubrum on soy and keratin protein displayed the activation of a large set of genes that encode secreted endo-and exoproteases. In addition, other specifically induced factors potentially implicated in protein utilization were identified, including heat shock proteins, transporters, metabolic enzymes, transcription factors, and hypothetical proteins with unknown functions. Of particular interest is the strong upregulation of key enzymes of the glyoxylate cycle in T. rubrum during growth on soy and keratin, namely, isocitrate lyase and malate synthase. This broad-scale transcriptional analysis of dermatophytes during growth on proteins reveals new putative pathogenicityrelated host adaptation mechanisms of these human pathogenic fungi.Dermatophytes are highly specialized fungi which are the most common agents of superficial mycoses in humans and animals (13, 34). Among the human pathogenic dermatophytes, the anthropophilic species Trichophyton rubrum is clinically the most commonly observed. In contrast to most other medically important fungi, dermatophytes are not opportunists but are obligate pathogens, infecting exclusively the skin stratum corneum, nails, or hair. The ability of dermatophytes to degrade and utilize compact hard keratin within such host structures is presumably related to their common secreted keratinolytic activity, which is therefore a major putative virulence attribute of these fungi. Individual endo-and exoproteases secreted by dermatophytes are similar to those of species of the genus Aspergillus. However, in contrast to those of Aspergillus spp., dermatophyte-secreted endoproteases are multiple and members of two large protein families, the subtilisins (Subs) S8 (serine proteases) and the fungalysins M36 (metalloproteases) (see the MEROPS peptidase database, http://merops.sanger.ac.uk) (10, 11). More than 20 genes that encode secreted proteases have been identified in dermatophytes, some of which have been characterized in detail on the molecular level (reviewed in reference 23).In order to better understand the basic mechanisms of protein degradation by dermatophytes, the secretome of different dermatophyte species was previously analyzed during in vitro growt...

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“…These two proteins are also essential for the fungicidal activity of human ␤-defensins 2 and 3 (491). C. albicans expresses a single Hsp90 isoform that is induced at the transition from yeast to filamentous growth, and deletion attenuates the virulence of the fungus in a murine model (43,415,451). A series of reports over the last decade have highlighted the role of Hsp90 in promoting drug resistance in C. albicans.…”

Section: The Hsr In Pathogenic Fungimentioning

confidence: 99%

Biology of the Heat Shock Response and Protein Chaperones: Budding Yeast (Saccharomyces cerevisiae) as a Model System

Verghese

Abrams

Wang

et al. 2012

Microbiol Mol Biol Rev

504

410

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SUMMARY The eukaryotic heat shock response is an ancient and highly conserved transcriptional program that results in the immediate synthesis of a battery of cytoprotective genes in the presence of thermal and other environmental stresses. Many of these genes encode molecular chaperones, powerful protein remodelers with the capacity to shield, fold, or unfold substrates in a context-dependent manner. The budding yeast Saccharomyces cerevisiae continues to be an invaluable model for driving the discovery of regulatory features of this fundamental stress response. In addition, budding yeast has been an outstanding model system to elucidate the cell biology of protein chaperones and their organization into functional networks. In this review, we evaluate our understanding of the multifaceted response to heat shock. In addition, the chaperone complement of the cytosol is compared to those of mitochondria and the endoplasmic reticulum, organelles with their own unique protein homeostasis milieus. Finally, we examine recent advances in the understanding of the roles of protein chaperones and the heat shock response in pathogenic fungi, which is being accelerated by the wealth of information gained for budding yeast.

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Fungal heat-shock proteins in human disease

Cited by 135 publications

References 445 publications

Combined Effect of Heat, Essential Oils and Salt on the Fungicidal Activity against Trichophyton mentagrophytes in Foot Bath

Combined Effect of Heat, Essential Oils and Salt on the Fungicidal Activity against Trichophyton mentagrophytes in Foot Bath

Gene Expression Profiling in the Human Pathogenic Dermatophyte Trichophyton rubrum during Growth on Proteins

Biology of the Heat Shock Response and Protein Chaperones: Budding Yeast (Saccharomyces cerevisiae) as a Model System

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