bromochloroacetic-acid and Tinea

Dermatophytes are the most common cause of superficial fungal infections (tinea infections) and are a specialized group of filamentous fungi capable of infecting and degrading keratinised tissues, including skin, hair, and nail. Essential to their pathogenicity and virulence is the production of a broad spectrum of proteolytic enzymes and other key proteins involved in keratin biodegradation and utilization of its breakdown products. The initial stage of biodegradation of native keratin is considered to be sulfitolysis, in which the extensive disulfide bridges present in keratin are hydrolyzed, although some secreted subtilisins can degrade dye-impregnated keratin azure without prior reduction (Sub3 and Sub4). Sulfitolysis facilitates the extracellular biodegradation of keratin by the dermatophytes' extensive array of endo- and exoproteases. The importance of dermatophyte proteases in infection is widely recognized, and these enzymes have also been identified as important virulence determinants and allergens. Finally, the short peptide and amino acid breakdown products are taken up by the dermatophytes, using as yet poorly characterised transporters, and utilized for metabolism. In this review, we describe the process of keratin biodegradation by dermatophytes, with an especial focus on recent developments in cutting edge molecular biology and '-omic' studies that are helping to dissect the complex process of keratin breakdown and utilization.

Topics: Arthrodermataceae; Gene Expression Regulation, Fungal; Genomics; Hydrogen-Ion Concentration; Hydrolysis; Keratins; Peptide Hydrolases; Protein Transport; Tinea; Virulence

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

The genera Trichophyton, Microsporum, and Epidermophyton include filamentous fungi that cause dermatophytosis, a superficial infection of the skin, stratum corneum, nail beds, and hair follicles. The ability of dermatophytes to adhere to these substrates and adapt to the host environment is essential for the establishment of infection. Several fungal enzymes and proteins participate in this adaptive response to the environment and to keratin degradation. Transcription factors such as PacC and Hfs1, as well as heat shock proteins, are involved in sensing and adapting to the acidic pH of the skin in the early stages of fungal-host interaction. During dermatophyte growth, with keratin as the sole carbon source, the extracellular pH shifts from acidic to alkaline. This creates an environment in which most of the known keratinolytic proteases exhibit optimal activity. These events culminate in the establishment and maintenance of the infection, which can be chronic or acute depending on the dermatophyte species. This review focuses on these and other molecular aspects of the dermatophyte-host interaction.

Topics: Animals; Epidermophyton; Host-Pathogen Interactions; Humans; Hydrolysis; Keratins; Microsporum; Tinea; Trichophyton

Keratin is a fibrous and recalcitrant structural protein and the third most abundant polymer in nature after cellulose and chitin. Subtilisin-like proteases (SUB) are a group of serine endoproteases, coded by seven genes (SUB1-7), which decompose keratin structures and have been isolated from dermatophytes. Herein, we identified the SUB genes in 30 clinical isolates of Trichophyton verrucosum obtained from human and animal dermatophytosis as well as asymptomatic animal carriers.. We designed and proposed a two-stage multiplex PCR technique to detect all seven genes encoding serine proteases in dermatophytes. The analysis revealed the presence SUB1 and SUB2 amplicons in all strains regardless of the host. In the group of isolates obtained from humans, all seven subtilisin genes were shown in 40% of the strains. In T. verrucosum from asymptomatic animals, none of the isolates showed the presence of all seven subtilisin genes, and only 30% had six genes. In turn, 10% of the isolates from symptomatic animals demonstrated all seven subtilisins amplicons.. In conclusion, the severity of infection and ability of T. verrucosum to cause dermatophytosis in humans may not be related to specific genes but their accumulation and synergistic effects of their products.. Dermatophytes are pathogenic filamentous fungi with capacity to attack keratinized structures such as skin, hair and nails, causing cutaneous superficial infections. Indeed, a biological characteristic of dermatophytes is their ability to invade keratin-rich tissues by producing enzymes. Various degrees of inflammatory responses can be induced exactly by the enzymes. Subtilisin-like proteases are endoproteases, which decompose keratin structures. Our study identifies SUB genes in clinical isolates of T. verrucosum obtained from human and animal dermatophytosis as well as asymptomatic animal carriers.

Topics: Animals; Arthrodermataceae; Genes, Fungal; Humans; Keratins; Multiplex Polymerase Chain Reaction; Skin; Subtilisin; Tinea

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

Terbinafine (Tbf) is a well-established anti-fungal agent used for management of a variety of dermal conditions including ringworm and athlete's foot. Both the biochemical mechanism of Tbf fungicidal action (based on squalene epoxidase inhibition) and the target region for Tbf in vivo (the stratum corneum (SC)) are well determined. However, the biochemical and pharmacokinetic approaches used to evaluate Tbf biochemistry provide no biophysical information about molecular level physical changes in the SC upon Tbf binding. Such information is necessary for improved drug and formulation design. IR spectroscopic methods were used to evaluate the effects of Tbf on keratin structure in environments commonly used in pharmaceutics to mimic those in vivo. The Amide I and II spectral regions (1500-1700 cm

Topics: Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratins; Protein Conformation, beta-Strand; Skin; Skin Abnormalities; Squalene Monooxygenase; Terbinafine; Tinea; Tinea Pedis

The filamentous fungus Trichophyton rubrum is a pathogen that causes superficial mycoses in humans, predominantly in keratinized tissues. The occurrence of dermatophytoses has increased in the last decades, mainly in immunocompromised patients, warranting research on the mechanisms involved in dermatophyte virulence. The genomes of dermatophytes are known to be enriched in genes coding for proteins containing the LysM domain, a carbohydrate-binding module, indicating the possible involvement of these genes in virulence. Although the LysM domains have already been described in other fungi, their biological functions in dermatophytes are unknown. Here we assessed the transcription of genes encoding proteins containing the LysM domains in T. rubrum grown on different substrates using quantitative real-time polymerase chain reaction. Some of these genes showed changes in transcription levels when T. rubrum was grown on keratin. In silico analyses suggest that some of these proteins share features, namely, they are anchored in the plasma membrane and contain the catalytic domain chitinase II and signal peptide domains. Here we show a detailed study of genes encoding the proteins with LysM-containing domains in T. rubrum, aiming to contribute to the understanding of their functions in dermatophytes.

Topics: Carbohydrate Metabolism; Chitinases; Computational Biology; Culture Media; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Humans; Keratins; Protein Sorting Signals; Tinea; Trichophyton

Trichophyton rubrum is the main etiological agent of skin and nail infections worldwide. Because of its keratinolytic activity and anthropophilic nature, infection models based on the addition of protein substrates have been employed to assess transcriptional profiles and to elucidate aspects related to host-pathogen interactions. Chalcones are widespread compounds with pronounced activity against dermatophytes. The toxicity of trans-chalcone towards T. rubrum is not fully understood but seems to rely on diverse cellular targets. Within this context, a better understanding of the mode of action of trans-chalcone may help identify new strategies of antifungal therapy and reveal new chemotherapeutic targets. This work aimed to assess the transcriptional profile of T. rubrum grown on different protein sources (keratin or elastin) to mimic natural infection sites and exposed to trans-chalcone in order to elucidate the mechanisms underlying the antifungal activity of trans-chalcone.. Overall, the use of different protein sources caused only slight differences in the transcriptional profile of T. rubrum. The main differences were the modulation of proteases and lipases in gene categories when T. rubrum was grown on keratin and elastin, respectively. In addition, some genes encoding heat shock proteins were up-regulated during the growth of T. rubrum on keratin. The transcriptional profile of T. rubrum exposed to trans-chalcone included four main categories: fatty acid and lipid metabolism, overall stress response, cell wall integrity pathway, and alternative energy metabolism. Consistently, T. rubrum Mapk was strongly activated during the first hours of trans-chalcone exposure. Noteworthy, trans-chalcone inhibited genes involved in keratin degradation. The results also showed effects of trans-chalcone on fatty acid synthesis and metabolic pathways involved in acetyl-CoA supply.. Our results suggest that the mode of action of trans-chalcone is related to pronounced changes in fungal metabolism, including an imbalance between fatty acid synthesis and degradation that interferes with cell membrane and cell wall integrity. In addition, this compound exerts activity against important virulence factors. Taken together, trans-chalcone acts on targets related to dermatophyte physiology and the infection process.

Topics: Antifungal Agents; Cell Wall; Chalcone; Elastin; Fatty Acids; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Humans; Keratins; Signal Transduction; Tinea; Trichophyton; Virulence Factors

Onychomycosis is a nail fungal infection, mostly caused by dermatophytes. The treatment efficacy is impaired by difficulties of reaching effective drug levels at the site of infection; frequent relapses occur after cessation of antifungal therapy. The aim of the study was to compare two commercial products containing ciclopirox or efinaconazole for antimycotic activity and antifungal drug resistance. A study of permeation and penetration through bovine hoof membranes, as a nail model, was performed to evaluate the antimycotic activity of permeates against clinical isolates of selected fungi, and the frequency of spontaneous

Topics: Animals; Antifungal Agents; Biological Transport; Cattle; Ciclopirox; Drug Resistance, Fungal; Hoof and Claw; Humans; Keratins; Microbial Sensitivity Tests; Microtomy; Models, Biological; Mutation; Nails; Permeability; Protein Binding; Tinea; Triazoles; Trichophyton

Trichophyton rubrum is a cosmopolitan filamentous fungus that can infect human keratinized tissue (skin, nails and, rarely, hair) and is the major agent of all chronic and recurrent dermatophytoses. The dermatophyte infection process is initiated through the release of arthroconidial adhesin, which binds to the host stratum corneum. The conidia then germinate, and fungal hyphae invade keratinized skin structures through the secretion of proteases. Although arthroconidia play a central role in pathogenesis, little is known about the dormancy and germination of T. rubrum conidia and the initiation of infection. The objective of this study was to evaluate the transcriptional gene expression profile of T. rubrum conidia during growth on keratin- or elastin-containing medium, mimicking superficial and deep dermatophytosis, respectively.. A transcriptional profiling analysis was conducted using a custom oligonucleotide-based microarray by comparing T. rubrum conidia grown on elastin and keratin substrates. This comparison shows differences according to protein source used, but consisted of a very small set of genes, which could be attributed to the quiescent status of conidia. The modulated genes were related to the dormancy, survival and germination of conidia, including genes involved in the respiratory chain, signal transduction and lipid metabolism. However, an induction of a great number of proteases occurred when T. rubrum was grown in the presence of keratin such as the subtilisin family of proteases (Sub 1 and Sub 3) and leucine aminopeptidase (Lap 1 and Lap 2). Interestingly, keratin also promoted the up-regulation of a gene encoding an adhesin-like protein with a tandem repeat sequence. In silico analysis showed that the protein contains a domain related to adhesin that may play a role in host-pathogen interactions. The expression of this adhesin-like gene was also induced during the co-culture of T. rubrum with a human keratinocyte cell line, confirming its role in fungal-host interactions.. These results contribute to the discovery of new targets involved in the adhesion of conidia and the maintenance of conidial dormancy, which are essential for triggering the process of infection and the chronicity of dermatophytosis.

Topics: Amino Acid Sequence; Cell Line; Coculture Techniques; Culture Media; Elastin; Fungal Proteins; Gene Expression Regulation, Fungal; Host-Pathogen Interactions; Humans; Keratinocytes; Keratins; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Spores, Fungal; Tinea; Transcriptome; Trichophyton

Onychomycosis is a common fungal nail disease that is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. Keratin affinity of topical drugs is an important physicochemical property impacting therapeutic efficacy. To be effective, topical drugs must penetrate the nail bed and retain their antifungal activity within the nail matrix, both of which are adversely affected by keratin binding. We investigated these properties for efinaconazole, a new topical antifungal for onychomycosis, compared with those of the existing topical drugs ciclopirox and amorolfine. The efinaconazole free-drug concentration in keratin suspensions was 14.3%, significantly higher than the concentrations of ciclopirox and amorolfine, which were 0.7% and 1.9%, respectively (P < 0.001). Efinaconazole was released from keratin at a higher proportion than in the reference drugs, with about half of the remaining keratin-bound efinaconazole removed after washing. In single-dose in vitro studies, efinaconazole penetrated full-thickness human nails into the receptor phase and also inhibited the growth of Trichophyton rubrum under the nail. In the presence of keratin, efinaconazole exhibited fungicidal activity against Trichophyton mentagrophytes comparable to that of amorolfine and superior to that of ciclopirox. In a guinea pig onychomycosis model with T. mentagrophytes infection, an efinaconazole solution significantly decreased nail fungal burden compared to that of ciclopirox and amorolfine lacquers (P < 0.01). These results suggest that the high nail permeability of efinaconazole and its potent fungicidal activity in the presence of keratin are related to its low keratin affinity, which may contribute to its efficacy in onychomycosis.

Topics: Administration, Topical; Animals; Antifungal Agents; Guinea Pigs; Humans; In Vitro Techniques; Keratins; Microbial Sensitivity Tests; Nails; Onychomycosis; Tinea; Triazoles; Trichophyton

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 pathogenicity-related host adaptation mechanisms of these human pathogenic fungi.

Topics: Arthrodermataceae; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Humans; Keratins; Molecular Sequence Data; Soybean Proteins; Tinea; Trichophyton

Dermatophytes are pathogenic fungi that infect human skin, nails and hair and cause dermatophytosis. Trichophyton mentagrophytes is one of the most widespread species that belong to this group. Infection of the skin tissues include several stages, i.e., adhesion to the surface of the skin, invasion into the sublayers by the penetration of fungal elements and secretion of enzymes that degrade the skin components. In this study we have followed the morphology of the fungal elements, such as arthroconidia and hyphae, during the adhesion and invasion stages. Skin explants were inoculated with the dermatophyte and observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Skin explants were also inoculated with a transgenic isolate of T. mentagrophytes expressing the green fluorescent protein (GFP). The infected sublayers were investigated by confocal scanning laser microscopy (CSLM). As an adaptation to the tissue environment, the dermatophyte produced long fibrils when it is on the open surface of the stratum corneum, while short and thin fibrils are produced inside the dense sublayers. The short and long projections might have a role in adhesion. Invasion may be produced by mechanical and biochemical means. Invasion of the tissue showed hyphal branching and growth in multiple directions. The proteolytic profile was assayed by substrate gel and proteolytic activity. Two serine proteases of similar molecular weight were secreted during growth on the epidermal matrix components keratin and elastin. The dermatophyte may use the proteolytic enzymes to invade the surface and also the deep layer of the skin in immunocompromised patients. Dermatophytes, which are well adapted infectious agents, seem to use their mechanical and biochemical capabilities to invade the skin tissue effectively.

Topics: Elastin; Electrophoresis, Polyacrylamide Gel; Genes, Reporter; Green Fluorescent Proteins; Humans; Hyphae; Keratins; Microscopy, Confocal; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Models, Biological; Peptide Hydrolases; Serine Endopeptidases; Skin; Tinea; Trichophyton

Tinea corporis is a superficial mycotic infection resulting in substantial epidermal changes. We determined skin barrier function, epidermal differentiation, and human-beta-defensin 2 (hBD-2) protein expression in 10 patients with tinea corporis caused by Trichophyton rubrum (T. rubrum). We found disturbed skin barrier function as shown by a significant increase in transepidermal water loss (TEWL) and specific ultrastructural changes including disturbed formation of extracellular lipid bilayers, lamellar body extrusion, and deposit of clotted material at the stratum granulosum/stratum corneum interface. Epidermal proliferation in tinea increased several fold and accordingly, proliferation and inflammation-associated keratins K6, K16, and K17 were expressed. Expression of basal keratins K5 and K14 increased, whereas differentiation-associated K10 was reduced. Reduction of the cornified envelope proteins involucrin, loricrin, and the S100 protein filaggrin was also seen. Reduced filaggrin expression correlated with reduced skin hydration; protein breakdown products of filaggrin have been shown to be important for water binding. Surprisingly, we found pronounced epidermal protein expression of hBD-2, which may be related to disturbed epidermal differentiation and inflammation. hBD-2 showed a weak, although significant, antifungal activity against T. rubrum in the turbidimetric assay and the immunohistological staining was somewhat less pronounced in areas directly underneath fungal hyphae in the stratum corneum. Together, we describe profound changes in skin barrier structure and function, epidermal proliferation, and differentiation including pronounced protein expression of hBD-2 in tinea corporis.

Topics: beta-Defensins; Cell Differentiation; Cell Membrane Permeability; Cell Proliferation; Dehydration; Epidermis; Filaggrin Proteins; Gene Expression Regulation; Humans; Intermediate Filament Proteins; Keratins; Membrane Proteins; Protein Precursors; Skin Physiological Phenomena; Tinea; Trichophyton

Trichophyton rubrum is a cosmopolitan and anthropophilic fungus able to invade keratinized tissue, causing infection in human skin and nails. This work evaluated the changes in the extracellular pH during its growth in keratin (after 6, 12, 24, 48, 72h and 7 days) at initial pH 5.0. We observed a gradual increase of basal pH under keratin exposure when compared to glucose condition. Also, we identified 576T. rubrum transcripts differentially expressed by subtractive suppression hybridization (SSH) using conidia cultivated for 72h in keratin as tester, and cultivated in glucose as driver. The over-expression of 238 transcripts obtained under keratin condition was confirmed by macro-array dot-blot, revealing 28 unigenes. Putative proteins encoded by these genes showed similarity to fungi proteins involved in basic metabolism, growth and virulence, i.e., transporters ABC-MDR, MFS and ATPase of copper, NIMA interactive protein, Gag-Pol polyprotein, virulence factors serine-protease subtilisin and metalloprotease, cytochrome P450, GlcN-6-phosphate deaminase and Hsp30. The upregulation of T. rubrum genes encoding subtilisin, metalloprotease and Gag-Pol polyprotein was also validated by northern blot. The results of this study provide the first insight into genes differentially expressed during T. rubrum grown in keratin that may be involved in fungal pathogenesis.

Topics: Base Sequence; Blotting, Northern; Female; Humans; Hydrogen-Ion Concentration; Keratins; Molecular Sequence Data; RNA, Messenger; Tinea; Trichophyton

The therapeutic efficacy of KP-103, a triazole derivative, for 10 guinea pigs with interdigital tinea pedis or tinea corporis was investigated. Topical KP-103 solution (0.25 to 1%) was dose-dependently effective in treating both dermatophytoses. A 1% KP-103-treatment rendered all infected skins culture-negative on day-2 posttreatment. A high negative-culture rate was obtained with 1% solutions of butenafine and lanoconazole but not with 1% neticonazole solution. The follow up study performed on day-30 and day-9 posttreatment demonstrated that the relapse rates for 1% KP-103-treated animals with tinea pedis and for those with tinea corporis were 20 and 30%, respectively, and that these values were the same as those for 1% butenafine-treated animals, but lower than those for 1% lanoconazole-treated animals (55 and 80%, respectively). When a single dose of 1% KP-103 was applied to the back skin 48 hr before fungal inoculation, 9 of the 10 animals were protected from the dermatophytosis, suggesting that active KP-103 is retained in skin tissue for at least 48 hr after dosing. Moreover, it was suggested that KP-103 retains a high activity in the horny layer because of its lower keratin-affinity. The effectiveness of KP-103 against dermatophytoses may be due to the favorable pharmacokinetic properties in the skin tissues, together with its potent antifungal activity.

Topics: Animals; Antibiotic Prophylaxis; Antifungal Agents; Aspergillus flavus; Disease Models, Animal; Drug Evaluation, Preclinical; Guinea Pigs; Keratins; Male; Microbial Sensitivity Tests; Secondary Prevention; Tinea; Tinea Pedis; Toes; Treatment Outcome; Triazoles; Trichophyton

Keratin particles impregnated with amorolfine or clotrimazole in serial doubling dilutions (64 to 0.125 microg/ml) were used to evaluate the activities of these agents against 20 isolates each of Trichophyton mentagrophytes and Trichophyton rubrum in a yeast carbon broth medium incorporating Alamar Blue dye. The proposed MIC with keratin impregnation (MIC(K)) is defined as the lowest concentration of an agent used to impregnate keratin particles that effects a fluorescence-based fungal growth quotient of 0.05 or less. The conventional colorimetric and visual MICs of amorolfine for the dermatophytes, 64 microg/ml] and 64 microg/ml [range, 16 to >64 microg], respectively) may indicate the strong in vivo antidermatophytic activity of amorolfine as a topical agent. The new antidermatophytic susceptibility testing procedure has potential clinical utility for the in vitro screening of agents for use in the topical treatment of superficial mycoses.

Topics: Antifungal Agents; Clotrimazole; Coloring Agents; Culture Media; Fluorometry; Humans; Keratins; Microbial Sensitivity Tests; Morpholines; Tinea; Trichophyton

From 60 horses showing skin lesions, 42% were positive for fungal infection. Horses less than 2-year old were more susceptible to this infection. Fourteen species belonging to nine genera of keratinophilic and cycloheximide-resistant fungi were recovered from collected specimens. Trichophyton was the dominant genus of which T. equinum was the most common. This species proved to be the main causative agent of ringworm in horses. In addition to dermatophytes, many species of the isolated fungi were keratinophilic. The presence of such fungi on hairs and skin of horses may create an opportunity for them under special circumstances to become invasive to the skin or hair and thus cause primary or secondary infection of the animals.

Topics: Animals; Arthrodermataceae; Egypt; Fungi; Horse Diseases; Horses; Keratins; Microsporum; Tinea; Trichophyton

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

In order to investigate the morphology of fungi invading into the human hair tissue, three cases of black dot ringworm caused by Trichophyton violaceum and Trichophyton glabrum were studied by light and electron microscopy. Fungal elements were mainly present in the hair cortex and showed a constant morphologic change during the differentiation of hair layers. The fungal elements, located deep in the keratogenous zone of the cortex, showed less electron dense non-septate hyphae. Distally, the hyphae showed septation and contained several scattered dense bodies in the cytoplasm. At the level where the Huxley's layer was keratinized, the fungal elements were transformed into arthrospores, which occupied the large volume of the cortex; each spore was surrounded by a fiber- and melanosome-free, electron lucent halo. Fungal elements occasionally invaded the keratinized hair cuticle and keratinized inner root sheath in a few hair follicles. Fungi do not invade the hair germinative cells. There seems to be a distinct relationship between the morphology of the invading fungi and the cortical cell differentiation in black dot ringworm; a balance between the fungus proliferation and the cortical cell development may be present.

Topics: Aged; Female; Hair; Humans; Keratins; Microscopy, Electron; Scalp; Tinea

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

The production of proteases was investigated during growth of dermatophytic fungi with special emphasis on Trichophyton rubrum. Exogenous glucose suppressed elastase production in all dermatophytes examined. The production of protease active guinea pig hair in keratin-salts broth by Microsporum gypseum. Trichophyton mentagrophytes and T. rubrum was also suppressed by glucose. Various carbohydrates added to keratin-salts broth curtailed protease production by T. rubrum as did individual amino acids but ammonium phosphate did not. Enzyme activities against guinea pig hair were compared in twenty-one diverse clinical isolates of T. rubrum cultured in keratin-salts broth. Activity also occurred towards casein, bovine serum albumin, keratin, collagen and elastin after keratin-growth. Studies concerning the properties of enzyme activities in culture filtrates of T. rubrum after keratin-growth suggested that multiple proteases occurred here. Hydrolysis of guinea pig hair and elastin were optimal at pH7 while keratinase was most active at alkaline pH. Divalent cations stimulated protease(s). Ferric ion and mercuric ion stimulated keratinase but were inhibitory to guinea pig hair hydrolysis and elastase. Chelating agents inhibited elastase and the hydrolysis of guinea pig hair more severely than keratinase and all of those effects were reversed by excess calcium. A serine-protease inhibitor, phenylmethylsulfonylfluoride (PMSF), curtailed keratinase but was less inhibitory to elastase and guinea pig hair hydrolysis. Soybean trypsin inhibitor arrested each protease.

Topics: Animals; Arthrodermataceae; Cell-Free System; Egtazic Acid; Elastin; Enzyme Repression; Glucose; Guinea Pigs; Hair; Humans; Hydrogen-Ion Concentration; Hydrolysis; Keratins; Metals; Peptide Hydrolases; Protease Inhibitors; Species Specificity; Tinea; Trichophyton

The rate of epidermal cell renewal in normal bovine skin and that reinoculated with Trichophyton verrucosum was measured using a radioautographic technique. The transit times of both nucleated and fully keratinised cells were measured in sequential biopsy samples removed at predetermined periods after intradermal inoculation with radio-labelled isotopes. The total time taken for cells of the basal layer to travel to the point of desquamation in the stratum corneum was 18 days in normal cattle. In similar areas on cattle that had been reinoculated with T verrucosum the total epidermal cell renewal time was reduced to 12 days. Increased protein synthesis, as measured by incorporation of radio-labelled nucleoside was evident in basal cells within 24 h of reinoculation with the fungus. The nucleated epidermal cell thickness had almost doubled in areas of reinoculated skin within 72 h and increased cell proliferation was maintained for at least 10 days. Desquamation of the thickened stratum corneum had occurred within seven days of reinoculation with the fungus.

Topics: Animals; Cattle; Cattle Diseases; Keratins; Skin; Tinea

Topics: Aged; Animals; Culture Media; Female; Guinea Pigs; Hair; Horses; Humans; Keratins; Male; Microsporum; Middle Aged; Mitosporic Fungi; Ontario; Soil Microbiology; Species Specificity; Tinea; Trichophyton

Topics: Animals; Hair; Keratins; Male; Microscopy, Electron; Tinea; Trichophyton

Topics: Agar; Ascomycota; Asparagine; Conjugation, Genetic; Culture Media; Hair; Humans; Keratins; Phenylalanine; Pigments, Biological; Quinic Acid; Shikimic Acid; Stereoisomerism; Tinea; Trichophyton; Tyrosine; Urease

Topics: Absorption; Administration, Oral; Adsorption; Animals; Cell-Free System; Griseofulvin; Guinea Pigs; Hair; Hydrolysis; Keratins; Peptide Hydrolases; Tinea; Trichophyton

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: Adult; Animals; Chymotrypsin; Electrophoresis, Polyacrylamide Gel; Humans; Immune Sera; Immunoelectrophoresis; Infant, Newborn; Keratins; Macroglobulins; Protease Inhibitors; Rabbits; Tinea; Trichophyton; Trypsin Inhibitors

Topics: Age Factors; Animal Nutritional Physiological Phenomena; Animals; Cattle; Cattle Diseases; Female; Hair; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Keratins; Skin; Skin Tests; Tinea; Trichophyton

Topics: Agar; Animals; Bahamas; Glucose; Hair; Horses; Humans; Keratins; Microsporum; Penicillium; Soil Microbiology; Tinea; Trichophyton

Topics: Animals; Culture Media; Genetic Variation; Genetics, Microbial; Hoof and Claw; Horses; Humans; Keratins; Tinea; Trichophyton

Topics: Antifungal Agents; Arthrodermataceae; Disease Reservoirs; Drug Resistance, Microbial; History, 19th Century; History, 20th Century; Humans; Keratins; Tinea

Fourteen cases are described in which the local application of corticosteroid preparations to ringworm infections of the skin have resulted in unusual clinical pictures. A kerion-like lesion due to Trichophyton rubrum, intertriginous infections simulating candidiasis and due to Epidermophyton floccosum, and pictures resembling poikiloderma, papular rosacea, and indeterminate leprosy are among the changes that were seen in these patients.

Topics: Adolescent; Adult; Aged; Betamethasone; Diagnosis, Differential; Eczema; Epidermophyton; Female; Fluocinolone Acetonide; Glucocorticoids; Griseofulvin; Humans; Keratins; Male; Middle Aged; Skin Diseases; Tinea; Triamcinolone Acetonide; Trichophyton; Valerates

Topics: Animals; Arthrodermataceae; Cattle; Dogs; Epidermophyton; Guinea Pigs; Hair; Horses; Humans; Keratins; Mice; Microsporum; Sheep; Tinea; Trichophyton

Topics: Arthrodermataceae; Dermatomycoses; Humans; Keratins; Tinea

Topics: Adolescent; Child; Drug Therapy; Geriatrics; Griseofulvin; Keratins; Leg Ulcer; Neurodermatitis; Pharmacology; Psoriasis; Tinea