bromochloroacetic-acid and Dermatomycoses

Dermatophytosis is a skin infection caused by keratinophilic, filamentous fungi. These are highly prevalent, common mycoses, affecting approximately 20% of the population. These fungi invade the stratum corneum, and other keratinised tissues, like nails and hair, where they grow by secreting enzymes and degrading keratin to obtain nutrients. Clinical presentation is variable and may depend on many factors, such as the infection site, the host's immunity and the dermatophyte's virulence. Generally, patients with acute superficial dermatophytosis mount cell-mediated immune responses. However, those suffering from chronic or recurrent infections are unable to develop this response, for reasons yet unknown. Several reports have described severe and occasionally life-threatening invasive diseases (deep dermatophytosis) associated with genetic mutations in the innate immunity-associated molecule CARD9, displaying the need to better understand its immune response. These dermatoses have substantial clinical consequences, producing chronic and difficult to treat skin lesions. They also lead to a decline in the patient's quality of life and impact their self-esteem. This review summarises findings on the immune response against dermatophytes.

Topics: Adaptive Immunity; CARD Signaling Adaptor Proteins; Dermatomycoses; Hair; Humans; Immunity; Immunity, Cellular; Immunity, Innate; Keratins; Nails; Opportunistic Infections; Skin; Trichophyton

Fungal infections of the skin, known as dermatophytoses, are initiated at the epidermal barrier and lead to dysfunctions of the stratum corneum and cornified skin appendages. Dermatophytosis affects a significant part of the human population and, despite the availability of effective treatments, its prevalence is still increasing. Numerous dermatophyte species are able to induce lesions in both animals and humans, with different clinical pictures and host inflammatory responses. The understanding of the infectious process and of tissue responses has been impeded by discrepancies between observations in vivo or in research models. Indeed, cells cultured as monolayers do not undergo the keratinization process required to study the adherence and invasion of dermatophytes. Animal models lack relevance to study human dermatophytosis because of species-specific differences in the development of lesions and inflammatory responses. This review focuses on the recent development of cultured human skin equivalents, which partly overcomes those limitations and allows improved understanding of the pathogenesis of dermatophytosis in human being, especially the impacts of infection on epidermal barrier integrity.

Topics: Animals; Arthrodermataceae; Dermatomycoses; Epidermis; Fungi; Genetic Predisposition to Disease; Humans; In Vitro Techniques; Keratins; Risk Factors; Skin; Skin Physiological Phenomena; Tinea; Trichophyton

Keratin is important and needed for the growth of dermatophytes in the host tissue. In turn, the ability to invade keratinised tissues is defined as a pivotal virulence attribute of this group of medically important fungi. The host-dermatophyte interaction is accompanied by an adaptation of fungal metabolism that allows them to adhere to the host tissue as well as utilize the available nutrients necessary for their survival and growth. Dermatophyte infections pose a significant epidemiological and clinical problem. Trichophyton rubrum is the most common anthropophilic dermatophyte worldwide and its typical infection areas include skin of hands or feet and nail plate. In turn, Microsporum canis is a zoophilic pathogen, and mostly well known for ringworm in pets, it is also known to infect humans. The aim of the study was to compare the intracellular metabolite content in the T. rubrum and M. canis during keratin degradation using liquid chromatography system coupled with tandem mass spectrometer (LC-MS/MS). The metabolite "fingerprints" revealed compounds associated with amino acids metabolism, carbohydrate metabolism related to the glycolysis and the tricarboxylic acid cycle (TCA), as well as nucleotide and energy metabolism. The metabolites such as kynurenic acid, L-alanine and cysteine in case of T. rubrum as well as cysteine and riboflavin in case of M. canis were detected only during keratin degradation what may suggest that these compounds may play a key role in the interactions of T. rubrum and M. canis with the host tissue. The metabolomic results were completed by qPCR gene expression assay. Our findings suggest that metabolomic analysis of T. rubrum and M. canis growing in culture media that mimic the dermatophyte infection could allow the understanding of processes involved in the pathogenesis of dermatophytes.

Topics: Arthrodermataceae; Chromatography, Liquid; Dermatomycoses; Keratins; Metabolomics; Microsporum; Skin; Tandem Mass Spectrometry; Tinea; Trichophyton

Trichophyton rubrum is the most common aetiological agent of human dermatophytoses. These infections mainly occur in keratinised layers such as skin, hair and nails because the fungus uses keratin as a nutrient source. Fluconazole and amphotericin are antifungal agents most commonly used to treat dermatophytoses and acts on cell membrane ergosterol. Despite the clinical importance of T rubrum, the mechanisms underlying the fungal-host relationship have not yet been clarified. Tandem repeats (TRs) are short DNA sequences that are involved in a variety of adaptive functions, including the process of fungal infection. It is known that the larger the number of TRs in the genome, the greater the capacity of cell-cell junction and surface adhesion, especially when these repeats are present in regions encoding cell surface proteins.. To identify in silico T rubrum genes containing TR patterns and to analyse the modulation of these genes in culture medium containing keratin (a model simulating skin infection) and antifungal drugs.. The Dermatophyte Tandem Repeats Database (DTRDB) and the FaaPred tool were used to identify four T rubrum genes containing TR patterns. Quantitative real-time (RT) PCR was used to evaluate the gene expression during the growth of T rubrum on keratin and in the presence of fluconazole, amphotericin B and Congo red (acts in the cell wall).. The expression of these genes was found to be induced in culture medium containing keratin. In addition, these genes were induced in the presence of antifungal agents, especially fluconazole, indicating an adaptive response to the stress caused by this drug.. The results suggest an important role of genes containing TRs in the fungal-host interaction and in the susceptibility to inhibitory compounds, indicating these sequences as new potential targets for the development of antifungal agents.

Topics: Antifungal Agents; Arthrodermataceae; Culture Media; Dermatomycoses; Fungal Proteins; Gene Expression; Gene Expression Regulation, Fungal; Host Microbial Interactions; Humans; Keratins; Microbial Sensitivity Tests; Spores, Fungal; Tandem Repeat Sequences

Although dermatophytes are the most common agents of superficial mycoses in humans and animals, the molecular basis of the pathogenicity of these fungi is largely unknown. In vitro digestion of keratin by dermatophytes is associated with the secretion of multiple proteases, which are assumed to be responsible for their particular specialization to colonize and degrade keratinized host structures during infection. To investigate the role of individual secreted proteases in dermatophytosis, a guinea pig infection model was established for the zoophilic dermatophyte Arthroderma benhamiae, which causes highly inflammatory cutaneous infections in humans and rodents. By use of a cDNA microarray covering approximately 20-25 % of the A. benhamiae genome and containing sequences of at least 23 protease genes, we revealed a distinct in vivo protease gene expression profile in the fungal cells, which was surprisingly different from the pattern elicited during in vitro growth on keratin. Instead of the major in vitro -expressed proteases, others were activated specifically during infection. These enzymes are therefore suggested to fulfil important functions that are not exclusively associated with the degradation of keratin. Most notably, the gene encoding the serine protease subtilisin 6, which is a known major allergen in the related dermatophyte Trichophyton rubrum and putatively linked to host inflammation, was found to be the most strongly upregulated gene during infection. In addition, our approach identified other candidate pathogenicity-related factors in A. benhamiae, such as genes encoding key enzymes of the glyoxylate cycle and an opsin-related protein. Our work provides what we believe to be the first broad-scale gene expression profile in human pathogenic dermatophytes during infection, and points to putative virulence-associated mechanisms that make these micro-organisms the most successful aetiological agents of superficial mycoses.

Topics: Animals; Arthrodermataceae; Dermatomycoses; Female; Gene Expression Profiling; Gene Expression Regulation, Fungal; Guinea Pigs; Keratins; Oligonucleotide Array Sequence Analysis; Peptide Hydrolases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Fungal

Batrachochytrium dendrobatidis is a member of the phylum Chytridiomycota and the causative organism chytridiomycosis, a disease of amphibians associated with global population declines and mass mortality events. The organism targets keratin-forming epithelium in adult and larval amphibians, which suggests that keratinolytic activity may be required to infect amphibian hosts. To investigate this hypothesis, we tested 10 isolates of B. dendrobatidis for their ability to grow on a range of keratin-supplemented agars and measured keratolytic enzyme activity using a commercially available kit (bioMerieux API ZYM). The most dense and fastest growth of isolates were recorded on tryptone agar, followed by growth on frog skin agar and the slowest growth recorded on feather meal and boiled snake skin agar. Growth patterns were distinctive for each nutrient source. All 10 isolates were strongly positive for a range of proteolytic enzymes which may be keratinolytic, including trypsin and chymotrypsin. These findings support the predilection of B. dendrobatidis for amphibian skin.

Topics: Agar; Animals; Anura; Chytridiomycota; Culture Media; Dermatomycoses; Keratins; Peptide Hydrolases

Keratinolytic properties of two dermatophytes (Microsporum gypseum, Trichophyton mentagrophytes) and three moulds (Scopulariopsis brevicaulis, Alternaria alternata, Geotrichum candidum) isolated from diseased equine hooves were examined to improve the understanding of pathogenic mechanisms leading to equine onychomycosis. Equine hoof horn material and skin, as well as hoof keratin and dermal keratin extracted from corresponding tissues, were used as sole carbon and nitrogen sources in five test tubes for each fungus. Within 18 days, supernatants of all tubes were repeatedly examined for keratinolytic activity by SDS-PAGE and Western blot analysis. In addition, fungal growth rates were determined to identify the preferred tissue of the individual fungi. Among the fungi examined, M. gypseum was the most keratinolytic species, followed by T. mentagrophytes and S. brevicaulis. In the concentration applied, the moulds A. alternata and G. candidum showed minimal keratinolytic activity. With respect to growth rates, M. gypseum favoured hoof horn material, S. brevicaulis and G. candidum preferred skin as a keratin source, whereas for the other two fungi no clear preference was detectable.

Topics: Animals; Arthrodermataceae; Blotting, Western; Dermatomycoses; Electrophoresis, Polyacrylamide Gel; Foot Diseases; Hoof and Claw; Horse Diseases; Horses; Keratinocytes; Keratins; Species Specificity

Topics: Arthrodermataceae; Dermatomycoses; Epidermis; Humans; Keratins; Microsporum; Trichophyton

Four fungal species including two dermatophytes and two saprophytes were isolated from sewage sludge samples at Basrah (Iraq) they were tested for their degradative ability towards three types of keratin substrates (human hair, chicken feathers and wool). The rate of keratin degradation was expressed as weight loss over three weeks of incubation using a liquid culture medium. Human hair had the highest degradation rate by colonization of Chrysosporium pannicola and Microsporum gypseum at a rate of 62% and 48% respectively. Chicken feathers were highly degraded by Aspergillus flavus (32%) while wool degradation was highest by C. pannicola (45.5%) and Trichophyton mentagrophytes var. erinacei (38%). There was a significant difference (p < 0.001) in keratin substrate degradation rates by the examined fungi. Keratinase activity was highest for C. pannicola and M. gypseum in the culture medium baited with human hair. Aspergillus flavus revealed the highest activity of this enzyme in cultures amended with chicken feathers while T mentagrophytes var. erinacei showed highest keratinase activity in cultures with wool substrate. The amount of protein released into the culture medium varied among the tested fungi. The medium's alkalinity increased over incubation time from 6.5 to 7.8. Microscopic examination showed maceration of the keratin substrates by the fungi.

Topics: Arthrodermataceae; Culture Media; Dermatomycoses; Hair; Humans; Keratins; Peptide Hydrolases; Sewage

A total of 330 dust and soil samples collected from different sites at 13 elementary schools and seven public parks in the province of Isfahan, Iran were examined for the frequency of keratinophilic fungi by the hair-baiting technique. Two hundred and fourteen isolates of keratinophilic fungi belonging to seven species were identified. The most frequent isolate was Chrysosporium keratinophilum (54.2%). The frequency and distribution of these keratinophilic fungi are discussed in relation to the presence of children in these environments.

Topics: Child; Chrysosporium; Dermatomycoses; Dust; Hair; Humans; Iran; Keratins; Mitosporic Fungi; Schools; Soil Microbiology; Urban Health

A keratinolytic protease secreted by a feline clinical isolate of Microsporum canis cultivated in a broth containing feline keratin as the sole nitrogen source was purified from the culture filtrate by affinity chromatography on bacitracin-agarose and by hydrophobic chromatography on octyl-agarose. The enzyme had an apparent molecular mass of 43.5 kDa and the pI was 7.7. It had a significant activity against keratin azure, elastin-Congo red and denatured type I collagen (azocoll). Using the latter substrate, the optimum pH was around 8 and the apparent optimum temperature around 50 degrees C. The protease was strongly inhibited by 1,10-phenanthroline, phosphoramidon and EDTA. The first 13 N-terminal amino acid sequence showed a 61% homology with that of the extracellular metalloprotease of Aspergillus fumigatus and with the neutral protease I of A. oryzae, confirming that this 43.5 kDa keratinase is a metalloprotease. This keratinolytic metalloprotease could be a virulence-related factor involved in pathophysiological mechanisms of M. canis dermatophytosis.

Topics: Amino Acid Sequence; Animals; Cat Diseases; Cats; Dermatomycoses; Electrophoresis, Polyacrylamide Gel; Keratins; Metalloendopeptidases; Microsporum; Molecular Sequence Data

The keratinolytic activity of five species of the dermatophytes which include Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum audouinii and M. gypseum isolated from school children were tested using human hair as the substrate. M. gypseum was found to possess the highest keratinolytic activity with a net value of released protein being 78.8 ug/ml after five weeks of incubation. Also the net value of released protein for T. tonsurans, T. rubrum, T. mentagrophytes and M. audouinii were 55.5 ug/ml, 52.5 ug/ml, 43.8 ug/ml and 26.3 ug/\\ml respectively. Only T. mentagrophytes and M. gypseum were able to cause structural damage in form of perforations on the hair shaft. Also during the degradation of the hair, the pH of the basal medium for each dermatophyte increased. The increase in pH was highest in the medium with M. gypseum but lowest in that of M. audouinii.

Topics: Arthrodermataceae; Dermatomycoses; Hair; Humans; Hydrogen-Ion Concentration; Keratins; Microsporum; Peptide Hydrolases; Substrate Specificity; Trichophyton

Microsporum-canis-infected cats, especially the asymptomatic infected ones, are mainly responsible for the zoonotic disease. The important variability of the clinical signs in cats is poorly understood. Recently, a 31.5-kD keratinolytic subtilase was found to be a putative virulence factor.. To investigate the possible relationship between the clinical status of dermatophytic cats and the production of the keratinase.. Seven M. canis strains isolated either from clinically affected, asymptomatic infected or mechanical carrier cats were tested for the in vitro production of the enzyme. The immunohistochemical detection of the enzyme was also assessed in skin biopsies of 4 symptomatic and 7 asymptomatic naturally infected cats.. All the strains produced in vitro a 31.5-kD keratinolytic subtilase. The enzyme was present in all but 1 of the infected cats.. The production of the keratinase is not a factor directly responsible for the clinical picture seen in M.-canis-infected cats.

Topics: Animals; Cats; Dermatomycoses; Female; Hair Follicle; Immunohistochemistry; Keratins; Male; Microsporum; Oligopeptides; Phenylmethylsulfonyl Fluoride; Protease Inhibitors; Subtilisins

Several clinical syndromes are characterized by ectodermal dysplasia (ED) in association with clefting of the lip and/or palate. In these syndromes, alopecia is primarily due to abnormalities of the hair shaft associated with increased hair fragility. Scalp dermatitis is yet another peculiar finding, primarily seen in the ankyloblepharon-ED-clefting (AEC) syndrome. We report on a 16-year-old patient with ectrodactyly-ED-clefting (EEC) syndrome, who exhibited a scarring alopecia due to deep folliculitis. On scanning electron microscopy, irregular torsion and longitudinal grooving of the hair shaft (pili torti et canaliculi) were observed. Quantitative determinations of the elastic and viscous parameters of hair demonstrated a normal viscosity but a significantly reduced hair elasticity, indicating either an abnormal composition or a disordered arrangement of microfibrils within the apparently normal keratin matrix. In contrast to the erosive scalp dermatitis of early onset in the AEC syndrome, alopecia in this case of EEC syndrome demonstrated follicular scarring with onset during puberty. We question a possible role of the anatomical hair abnormality in the pathogenesis of chronic deep folliculitis in this and clinically related syndromes.

Topics: Adolescent; Alopecia; Biophysical Phenomena; Biophysics; Cicatrix; Cleft Lip; Cleft Palate; Dermatomycoses; Ectodermal Dysplasia; Elasticity; Fingers; Folliculitis; Hair; Humans; Keratins; Malassezia; Male; Microscopy, Electron, Scanning; Puberty; Scalp Dermatoses; Staphylococcal Skin Infections; Syndrome; Viscosity

Clinical reports of hereditary palmoplantar keratoderma are generally based on a limited number of patients. In 1967 the prevalence in the northernmost county of Sweden (Norrbotten) was shown to be 0.55%. In 1982 it was possible to trace half of the original propositi from that study. Among these families, a severe clinical form with a presumed recessive inheritance could be distinguished. The clinical pictures in relatives of the original propositi were described, and other diseases were listed together with those in patients from previously performed studies. The frequency of dermatophytosis was 36.2%, which was equal to a prevalence of 37.6%. T. mentagrophytes occurred significantly more often and immunological factors, such as increased presence of blood group A, specific dermatophyte IgG antibodies, precipitating antibodies and an immunological in vitro reaction to keratin, supported differences in the distribution of dermatophytes. However, the amount of keratin was considered the most important factor for the affinity of dermatophytes to the palms and soles. A vesicular eruption along the hyperkeratotic border and a mononuclear cell infiltrate were often reported. Such reactions were interpreted as immunological reactions to dermatophytosis. Scaling and fissuring were considered clinical signs of dermatophyte infections and not a part of the originally reported clinical picture. Results of the histopathological study corresponded to previously reported descriptions of the Unna-Thost variety. However, it has recently been reported that the histopathological picture of this variety was based on histopathological features of epidermolytic palmoplantar keratoderma. The existence on the Continent of the Unna-Thost variety was therefore questioned. Histopathological features of epidermolytic palmoplantar keratoderma were not found in the County of Norrbotten and the designation "Diffuse HPPK type Norrbotten" has therefore been proposed. The histopathological picture of the presumed recessive variety did not differ from that of the dominant variety but ultrastructural characteristics differentiated it from Mal de Meleda and the dominant variety. It was therefore concluded that a new variety with a presumed recessive inheritance was found.

Topics: ABO Blood-Group System; Adolescent; Adult; Aged; Antibodies, Fungal; Arthrodermataceae; Child; Child, Preschool; Dermatomycoses; Female; Foot Dermatoses; Genes, Dominant; Genes, Recessive; Hand Dermatoses; Humans; Immunoglobulin E; Immunoglobulin G; Infant; Keratins; Keratoderma, Palmoplantar; Male; Middle Aged; Pedigree; Sweden; Tinea; Trichophytin; Trichophyton

Fourteen patients with hereditary palmoplantar keratoderma of the Unna Thost variety were included in the study. Dermatophytosis was found in 7 of the 14 patients. Six were affected with T. rubrum and one with T. mentagrophytes. The growth pattern of dermatophytes in keratin from the patients did not differ from that of normal control individuals. Keratin from patients with hereditary palmoplantar keratoderma was sterilized with ethylene gas and placed in the center of culture plates, previously broad inoculated with control dermatophytes or dermatophytes isolated from patients. An inhibition zone around the keratin was found in 42.9% of the control dermatophytes and in 83.4% of the patient cultures. The inhibition zone was only seen in cultures with T. rubrum and not in those with T. mentagrophytes. No significant difference in minimal inhibitory concentration values against ketoconazole between control dermatophytes and dermatophytes from patients was demonstrated.

Topics: Adult; Aged; Arthrodermataceae; Candida albicans; Dermatomycoses; Female; Humans; Keratins; Keratoderma, Palmoplantar; Ketoconazole; Male; Middle Aged; Trichophyton

Soils rich in keratinic residues constitute a permanent or occasional reservoir for dermatophytes and keratinolytic and keratinophilic fungi, and are a source of potential infection for man and animals. The keratinolytic and keratinophilic mycoflora of 28 sandpits in Turin was studied to evaluate the risk of fungal skin infections that is run by children as they play in public parks and to lay the ground-work for a next epidemiological study of soil- and animal-inhabiting dermatophytes found in cities, and their impact on human dermatophytoses. Fifty seven species were isolated and a high percentage (52%) showed keratinolytic activity. Species of Microsporum, Trichophyton, Mariannaea, Aphanoascus, Chrysosporium, Malbranchea and Geomyces showed the most active keratinolysis.

Topics: Animals; Arthrodermataceae; Child; Dermatomycoses; Hair; Humans; Italy; Keratins; Risk; Soil Microbiology

The phenotypes of infiltrating cells and class II transplantation antigens on keratinocytes in candida and dermatophyte lesions from 15 patients were analysed in situ with an immunohistochemical double staining technique combined with periodic acid-Schiff staining. In five out of ten biopsies from candida lesions and in one of five biopsies from dermatophyte lesions the keratinocytes expressed HLA-DR but not HLA-DQ antigens. The HLA-DR expression was patchy in all and most pronounced in two candida biopsies which also contained large infiltrates of anti-Leu 3a reactive T lymphocytes. The induction of detectable amounts of different class II antigens on keratinocytes might depend on the type of antigen, the magnitude and duration of the response elicited and/or the immunological state of the patient.

Topics: Adult; Aged; Antibodies, Monoclonal; Biopsy; Candidiasis, Cutaneous; Dermatomycoses; Epidermal Cells; Epidermis; HLA-D Antigens; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Phenotype; Staining and Labeling; T-Lymphocytes; Tinea

Topics: Animals; Arthrodermataceae; Culture Media; Dermatomycoses; Epidermophyton; Humans; Keratins; Kinetics; Microsporum; Rabbits; Temperature; Trichophyton

Topics: Animals; Dermatomycoses; Endopeptidases; Gelatin; Humans; Keratins; Mice; Mitosporic Fungi; Soil Microbiology; Species Specificity

Topics: Animals; Australia; Dermatomycoses; Humans; Keratins; Microsporum; Soil Microbiology

Topics: Adolescent; Adult; Age Factors; Animals; Arthrodermataceae; Child; Child, Preschool; Dermatomycoses; Epidermophyton; Female; Hair; Humans; Infant; Keratins; Male; Microsporum; Middle Aged; Species Specificity; Trichophyton

Topics: Argentina; Arthrodermataceae; Dermatomycoses; Fungi; Humans; Keratins; Soil Microbiology

The in vitro ability of 5 Hendersonula toruloidea and 1 control Microsporum gypseum strain to degrade human hair has been studied by analysis of culture medium and microscopy. H. toruloidea was able to utilize human hair as a source of nutrients but the extent varied according to the isolate and in all cases degradation was less marked than with M. gypseum.

Topics: Adult; Dermatomycoses; Hair; Humans; Keratins; Male; Microsporum; Mitosporic Fungi; Species Specificity

Topics: Child; Cystine; Dermatomycoses; Disulfides; Esters; Hair; Humans; Hydrogen-Ion Concentration; Keratins; Methylation; Methylene Blue; Microsporum; Protein Denaturation; Staining and Labeling; Sulfates; Sulfites; Sulfonic Acids; Thiosulfates

Topics: Adolescent; Ascomycota; Child; Child, Preschool; Dermatomycoses; Female; Fungi; Health Surveys; Humans; India; Keratins; Male; Microsporum; Mitosporic Fungi; Onychomycosis; Rural Population; Seasons; Soil Microbiology; Tinea; Tinea Capitis; Tinea Pedis; Trichophyton; Urban Population

Topics: Animals; Arthrodermataceae; Dermatomycoses; Disease Reservoirs; Eulipotyphla; Fungi; Germany, East; Hair; Humans; Keratins; Mice; Skin; Statistics as Topic

Topics: Arthrodermataceae; Dermatomycoses; Humans; Keratins; Tinea

Topics: Arthrodermataceae; Dermatomycoses; Humans; Keratins; Pathology

Topics: Dermatomycoses; Fungi; Keratins; Skin; Soil; Soil Microbiology