ABSTRACT
Aim: The design, synthesis, docking studies and evaluation of the in vitro antifungal and cytotoxic properties of eugenol (EUG) containing 1,2,3-triazole derivatives are reported. Most of the derivatives have not been reported.Materials & methods: The EUG derivatives were synthesized, molecular docked and tested for their antifungal activity.Results: The compounds showed potent antifungal activity against Trichophyton rubrum, associated with dermatophytosis. Compounds 2a and 2i exhibited promising results, with 2a being four-times more potent than EUG. The binding mode prediction was similar to itraconazole in the lanosterol-14-α-demethylase wild-type and G73E mutant binding sites. Additionally, the pharmacokinetic profile prediction suggests good gastrointestinal absorption and potential oral administration.Conclusion: Compound 2a is a promising antifungal agent against dermatophytosis caused by T. rubrum.
[Box: see text].
Subject(s)
Antifungal Agents , Drug Design , Eugenol , Microbial Sensitivity Tests , Molecular Docking Simulation , Triazoles , Eugenol/pharmacology , Eugenol/chemistry , Eugenol/chemical synthesis , Eugenol/analogs & derivatives , Triazoles/chemistry , Triazoles/pharmacology , Triazoles/chemical synthesis , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Humans , Trichophyton/drug effects , Structure-Activity Relationship , Molecular StructureABSTRACT
The therapeutic potential of medicinal plants is known as an alternative in treatment of human affections; in effect, the conventional application of these medicinal sources has several limitations like low bioavailability, solubility and stability, which affect its pharmacological efficacy. In recent decades, extraordinary advances have been made in new drug delivery systems using nanocarriers. This work consisted in determining the in vitro antifungal activity of the methanolic extract of Euphorbia tirucalli formulated in polymeric nanoparticles. The antifungal activity was determined by the microdilution method in 96-well microplates, applying nanoparticles loaded with plant extract (NP-Ext) obtained by nanoprecipitation on clinical isolates of Trichophyton rubrum and T. interdigitalis. Regarding the nanoparticles, the lots used did not present significant differences in their physicochemical characteristics, with a size of 91.885 ± 1.621nm, polydispersity index of 0.152 ± 0.025 and Z-potential of -6.047 ± 0.987. The quantification of the extract in the polymeric matrix was determined by infrared spectroscopy (FTIR), where an efficiency and encapsulation percentage of 22.15 ± 0.82 and 2.95 ± 0.11, respectively, were obtained. The in vitro antifungal activity of the crude and formulated extract was obtained calculating the Minimum Inhibitory Concentration (MIC) of each one; a MIC of 125 µg/mL was obtained against T. rubrum and T. interdigitalis with the crude extract, while a MIC value of 55.55 and 0.1 µg/mL was obtained with NP-Ext, respectively, against these same. Conclusions: biological activity is closely linked to the phytochemical profile of the extract; while the improvement of said potential with the NP-Ext with the dosage form was directly related to the physicochemical characteristics of the nanocarrier.
Subject(s)
Antifungal Agents , Euphorbia , Microbial Sensitivity Tests , Nanoparticles , Plant Extracts , Euphorbia/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Nanoparticles/chemistry , Spectroscopy, Fourier Transform Infrared , Trichophyton/drug effects , Polymers/pharmacology , Polymers/chemistry , ArthrodermataceaeABSTRACT
Fungal infections have emerged worldwide, and azole antifungals are widely used to control these infections. However, the emergence of antifungal resistance has been compromising the effectiveness of these drugs. Therefore, the objective of this study was to evaluate the antifungal and cytotoxic activities of the nine new 1,2,3 triazole compounds derived from thymol that were synthesized through Click chemistry. The binding mode prediction was carried out by docking studies using the crystallographic structure of Lanosterol 14α-demethylase G73E mutant from Saccharomyces cerevisiae. The new compounds showed potent antifungal activity against Trichophyton rubrum but did not show relevant action against Aspergillus fumigatus and Candida albicans. For T. rubrum, molecules nº 5 and 8 showed promising results, emphasizing nº 8, whose fungicidal and fungistatic effects were similar to fluconazole. In addition, molecule nº 8 showed low toxicity for keratinocytes and fibroblasts, concluding that this compound demonstrates promising characteristics for developing a new drug for dermatophytosis caused by T. rubrum, or serves as a structural basis for further research.
Subject(s)
Antifungal Agents , Arthrodermataceae , Microbial Sensitivity Tests , Molecular Docking Simulation , Thymol , Triazoles , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Triazoles/pharmacology , Triazoles/chemistry , Humans , Thymol/pharmacology , Thymol/chemistry , Arthrodermataceae/drug effects , Arthrodermataceae/genetics , Candida albicans/drug effects , Candida albicans/genetics , Aspergillus fumigatus/drug effects , Aspergillus fumigatus/genetics , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/genetics , Keratinocytes/drug effects , Trichophyton/drug effects , Trichophyton/geneticsABSTRACT
Dermatomycosis is an infection with global impacts caused especially by dermatophytes and Candida species. Current antifungal therapies involve drugs that face fungal resistance barriers. This clinical context emphasizes the need to discover new antifungal agents. Herein, the antifungal potential of 10 curcumin analogs was evaluated against four Candida and four dermatophyte species. The most active compound, 3,3'-dimethoxycurcumin, exhibited minimum inhibitory concentration values ranging from 1.9â62.5 to 15.6â62.5 µg ml-1 against dermatophytes and Candida species, respectively. According to the checkerboard method, the association between DMC and terbinafine demonstrated a synergistic effect against Trichophyton mentagrophytes and Epidermophyton floccosum. Ergosterol binding test indicated DMC forms a complex with ergosterol of Candida albicans, C. krusei, and C. tropicalis. However, results from the sorbitol protection assay indicated that DMC had no effect on the cell walls of Candida species. The in vivo toxicity, using Galleria mellonella larvae, indicated no toxic effect of DMC. Altogether, curcumin analog DMC was a promising antifungal agent with a promising ability to act against Candida and dermatophyte species.
Subject(s)
Arthrodermataceae , Curcumin , Curcumin/analogs & derivatives , Antifungal Agents/pharmacology , Candida , Curcumin/pharmacology , Microbial Sensitivity Tests , Ergosterol , TrichophytonSubject(s)
Tinea , Trichophyton , Tinea/microbiology , Tinea/pathology , Tinea/drug therapy , Humans , Brazil , Animals , Trichophyton/isolation & purification , Guinea Pigs , Male , FemaleABSTRACT
Trichophyton species cause dermatophytosis in humans, with a high, worldwide frequency of reports and important public health relevance. We evaluated 61 Trichophyton strains from different sources deposited in the University Recife Mycology (URM) culture collection of the Universidade Federal de Pernambuco, Brazil. Strains were phenotypically identified and confirmed by sequencing Internal Transcribed Spacers rDNA and partial beta-tubulin 2-exon. Additionally, we evaluated their susceptibility to terbinafine and itraconazole. Physiological analyses included urease activity and growth in casein medium. Phenotypic methods allowed the reliable identification of T. rubrum only, whereas, for other species, molecular methods were mandatory. All Trichophyton species exhibited susceptibility profiles to itraconazole (0.04-5.33 µg/mL) and terbinafine (0.17-3.33 µg/mL). Our analyses revealed a heterogeneous distribution of T. mentagrophytes, which does not support the current distribution within the species complex of T. mentagrophytes and its genotypes.
Subject(s)
Arthrodermataceae , Tinea , Humans , Trichophyton , Terbinafine/pharmacology , Antifungal Agents/pharmacology , Itraconazole , Brazil , Universities , Microbial Sensitivity Tests , Arthrodermataceae/geneticsSubject(s)
Tinea Capitis , Child , Humans , Tinea Capitis/drug therapy , Trichophyton , Antifungal Agents/therapeutic useABSTRACT
Dermatomycoses are typical hair, skin, or nail infections caused mainly by dermatophytes and nondermatophytes: Trichophyton, Microsporum, Epidermophyton, and Candida. In addition to the esthetical impact, pain, and nail deformity, these mycoses can be a source of severe disease. The high cost of treatment, toxicity, and the emergence of resistant infectious agents justifies research into new drugs. This work evaluates the fungicidal activity of nanocomposites (NCs) based on reduced graphene oxide (rGO) loaded with silver (Ag) nanoparticles (rGO/Ag) against clinical isolates of dermatophytes and Candida species. This is an unprecedented study in which, for the first time, hybrid nanocompounds based on Ag/rGO were tested against Epidermophytom, Microsporum, and Trichophyton species (dermatophytes agents). In this paper, we synthesize rGO using different concentrations of Ag by hydrolysis of metal salt AgNO3 and follow the growth of nanocrystals on sheets of rGO provided by the NaBH4. The NCs were analyzed by X-ray diffraction analysis, and the NC morphology, silver distribution on the rGO surface, and crystalline information were investigated by transmission electron microscopy. Antifungal susceptibility assay was performed by the microdilution method based on modified Clinical and Laboratory Standards Institute (CLSI) protocol. Time-kill kinetics was conducted to monitor the effect of the composite to inhibit fungal cells or promote structural changes, avoiding germination. The toxicological evaluation of the NCs was born in an in vivo model based on Galleria mellonella (G. mellonella). Minimum inhibitory concentration (MIC) values of the rGO/Ag NCs ranged from 1.9 to 125 µg/mL. The best inhibitory activity was obtained for rGO/Ag12%, mainly against Candida spp. and Epidermophyton floccosum. In the presence of sorbitol, MIC values of rGO/Ag NCs were higher (ranging from 15.6 to 250 µg/mL), indicating the action mechanism on the cell wall. Both yeast and dermatophytes clinical isolates were inhibited at a minimum of 6 and 24 h, respectively, but after 2 and 12 h, they had initial antifungal interference. All hybrid formulations of rGO/Ag NCs were not toxic for G. mellonella. This study provides insights into an alternative therapeutic strategy for controlling dermatomycoses.
Subject(s)
Arthrodermataceae , Dermatomycoses , Nanocomposites , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida , Silver/pharmacology , Trichophyton , Dermatomycoses/drug therapyABSTRACT
INTRODUCTION: The Trichophyton rubrum complex comprises the majority of dermatophyte fungi (DM) responsible for chronic cases of onychomycosis, which is treated with oral or topical antifungals. However, owing to antifungal resistance, alternative therapies, such as photodynamic therapy (PDT), are needed. This study investigated the frequency of the T. rubrum species complex in onychomycosis cases in the northwestern region of Paraná state, Brazil, and evaluated the efficacy of (PDT) using P123-encapsulated hypericin (Hyp-P123) on clinical isolates of T. rubrum in the planktonic cell and biofilm forms. MATERIAL AND METHODS: The frequency of the T. rubrum complex in onychomycosis cases from 2017 to 2021 was evaluated through a data survey of records from the Laboratory of Medical Mycology (LEPAC) of the State University of Maringa (UEM). To determine the effect of PDT-Hyp-P123 on planktonic cells of T. rubrum isolates, 1 × 105 conidia/mL were treated with ten different concentrations of Hyp-P123 and then irradiated with 37.8 J/cm2. Antibiofilm activity of PDT-Hyp-P123 was tested against T. rubrum biofilm in the adhesion phase (3 h), evaluated 72 h after irradiation (37.8 J/cm2), and the mature biofilm (72 h), evaluated immediately after irradiation. In this context, three different parameters were evaluated: cell viability, metabolic activity and total biomass. RESULTS: The T. rubrum species complex was the most frequently isolated DM in onychomycosis cases (approximately 80 %). A significant reduction in fungal growth was observed for 75 % of the clinical isolates tested with a concentration from 0.19 µmol/L Hyp-P123, and 56.25 % had complete inhibition of fungal growth (fungicidal action); while all isolates were azole-resistant. The biofilm of T. rubrum isolates (TR0022 and TR0870) was inactivated in both the adhesion phase and the mature biofilm. CONCLUSION: PDT-Hyp-P123 had antifungal and antibiofilm activity on T. rubrum, which is an important dermatophyte responsible for onychomycosis cases.
Subject(s)
Onychomycosis , Photochemotherapy , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Onychomycosis/drug therapy , Onychomycosis/microbiology , Photochemotherapy/methods , Azoles/pharmacology , Azoles/therapeutic use , Trichophyton , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , BiofilmsABSTRACT
BACKGROUND: Dermatophytosis is one of the most common fungal infections worldwide. The distribution of dermatophytes varies across continents, but the genera Trichophyton and Microsporum have emerged as the main isolated agents in humans and animals. OBJECTIVES: To validate Drosophila melanogaster flies as a fast and feasible model to study dermatophytic infections. METHODS: Wild-type (WT) and Toll-deficient D. melanogaster flies were infected by Trichophyton rubrum, T. mentagrophytes, Microsporum canis and Nannizzia gypsea by pricking with a needle previously dipped in inoculum concentrations ranging from 103 to 108 colony-forming units/mL. Establishment of infection was confirmed by survival curves, histopathological analysis and fungal burden. Thereafter, flies were treated with terbinafine, itraconazole and clioquinol. RESULTS: WT flies were predominantly resistant to the infection, whereas Toll-deficient flies succumbed to the four dermatophyte genera tested. The antifungal drugs protected flies from the infection, except for N. gypsea whose survival curves did not differ from the untreated group. CONCLUSIONS: This pilot study confirms that D. melanogaster is a suitable model to study the virulence and antifungal drug efficacy in dermatophyte species.
Subject(s)
Arthrodermataceae , Tinea , Humans , Animals , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Drosophila melanogaster , Pilot Projects , Itraconazole , Trichophyton , Tinea/drug therapy , Tinea/microbiologyABSTRACT
Trichophyton, Microsporum, Nannizzia and Epidermophyton genera cause dermatophytosis, the most common and highly contagious infectious skin disease. Rio de Janeiro is one of the most visited cities in the Southern Hemisphere, located in the most visited state of Brazil. This retrospective study investigated epidemiological and laboratorial aspects of dermatophytosis in Rio de Janeiro state, Brazil, by using spatiotemporal analysis. More than half of all individuals were infected by one or more dermatophytes. A variation between 18 and 106 years-old of the studied population was verified, and women more frequently affected. Patients were more frequently infected by Trichophyton spp., most of them T. rubrum, followed by T. mentagrophytes. M. canis and N. gypsea were more frequently isolated in the age group between 40 and 60 years old, while T. rubrum predominates among younger patients. All species presented homogeneous distribution while T. tonsurans appears to be restricted to the Rio de Janeiro capital and E. floccosum to the municipality of Macaé (190 Km apart from RJ). Rio de Janeiro state presented spatial clusters of dermatophytosis with high density in Guanabara Bay (E. floccosum, M. canis, N. gypsea, T. tonsurans) and Niterói (T. rubrum, T. mentagrophytes) but low density in Macaé (E. floccosum). Significant spatiotemporal clusters on dermatophytosis cases were detected in distinct municipalities (p-value ≤ 0.05). The Vulnerability Index (r = 0.293) and Demographic Density (r = 0.652) distributed according to neighborhoods in Niterói were direct related with dermatophytosis cases whereas Income (r = -0.306) was inversely correlated (p-value ≤ 0.05). The dermatophytosis spatiotemporal distinct distribution after two major international events in Rio de Janeiro, Brazil, highlight the pressing need for specific measures of its prevention and controlling. This is particularly relevant in touristic tropical localities which must consider both socio-economical and traveler's medicine variables.
Subject(s)
Arthrodermataceae , Canidae , Dermatomycoses , Tinea , Animals , Humans , Female , Adult , Middle Aged , Adolescent , Young Adult , Aged , Aged, 80 and over , Retrospective Studies , Tinea/epidemiology , Brazil/epidemiology , Trichophyton , MicrosporumABSTRACT
The classical dermatophytes diagnosis is based on mycological culture and microscopy observation both human and animal hair, skin, and nail samples. The aim of this work was to develop the new in-house real-time PCR with pan-dematophyte reaction for detection and identification of the main dermatophytes directly from hair samples, providing a simple and rapid diagnosis of dermatophytosis in dogs and cats. An in-house SYBR-Green real-time PCR was designed and used for detecting a DNA fragment encoding chitin synthase 1 (CHS1). A total of 287 samples were processed by culture, microscopic examination with KOH 10%, and real-time PCR (qPCR) analysis. Melting curve analysis of the CHS1 fragment revealed to be reproducible, showing a single distinct peak for each species of dermatophyte, namely Trichophyton mentagrophytes, T. verrucosum, Microsporum canis, and Nannizzia gypsea (formerly M. gypseum). Then, out of the 287 clinically suspected cases of dermatophytosis, 50% were positive for dermatophytes by qPCR, 44% by mycological culture, and 25% by microscopic examination. Microsporum canis was identified in 117 samples tested by culture and 134 samples tested by qPCR, followed by N. gypsea in 5 samples (either tested by culture or qPCR) and T. mentagrophytes detected in 4 and 5 samples when tested by culture or qPCR, respectively. Overall, qPCR allowed the diagnosis of dermatophytosis in clinical samples. The results suggest this newly proposed in-house real-time PCR assay can be used as alternative diagnosis and rapid identification of dermatophytes frequently associated to clinical hair samples of dogs and cats.
The aim of this work was to develop a molecular detection strategy for dermatophytes by SYBR-Green real-time PCR of hair samples from animals. The melting curve analysis of the CHS1 fragment revealed to be reproducible, showing a single distinct peak for distinct dermatophyte species and allowed the diagnosis of dermatophytosis in dogs and cats caused mainly by Trichophyton mentagrophytes, Microsporum sp., and Nannizzia gypsea).
Subject(s)
Arthrodermataceae , Cat Diseases , Dermatomycoses , Dog Diseases , Tinea , Cats , Animals , Dogs , Humans , Arthrodermataceae/genetics , Dermatomycoses/diagnosis , Dermatomycoses/veterinary , Real-Time Polymerase Chain Reaction/veterinary , Cat Diseases/diagnosis , Dog Diseases/diagnosis , Microsporum/genetics , Hair , Chitin Synthase/genetics , Tinea/veterinary , Trichophyton/geneticsABSTRACT
Wild animals can be natural reservoirs of different microorganisms, essential for monitoring these pathogens for the generation of knowledge and creation of tools aimed at programs for the prevention and control of infectious diseases, including zoonoses. The objective was to report the fungal diversity in the skin of pacas in captivity in Acre, Western Amazon, Brazil. Twenty-six animals were evaluated, from which skin samples were collected by superficial scraping, hair avulsion, and sterile plastic brush. The samples were seeded on Mycosel agar, and the phenotypic characteristics of the colonies were analyzed. In 80.8% of the samples, different fungi were isolated, from the genera Candida, Microsporum,and Trichophyton, among others. This is the first description of the identification of fungi in the skin of pacas and suggests that these animals can be considered essential reservoirs of saprophytic or pathogenic microorganisms with zoonotic potential in the Western Amazon.(AU)
Animais silvestres podem ser reservatórios naturais de diferentes microrganismos, sendo fundamental o monitoramento destes patógenos para a geração de conhecimento e criação de ferramentas direcionadas a programas de prevenção e controle de enfermidades infecciosas, incluindo as zoonoses. Assim, objetivou-se relatar a diversidade fúngica da pele de pacas criadas em cativeiro no Acre, Amazônia Ocidental, Brasil. Foram avaliados 26 animais, dos quais amostras cutâneas foram colhidas por raspagem superficial, avulsão pilosa e escova plástica estéril. As amostras foram semeadas em ágar Mycosel e as características fenotípicas das colônias foram analisadas. Em 80,8% das amostras houve isolamento de diferentes fungos, dos gêneros Candida, Microsporum e Trichophyton, dentre outros. Esta é a primeira descrição da identificação de fungos na pele de pacas e sugere que estes animais podem ser considerados importantes reservatórios de microrganismos saprófitas ou patogênicos, de potencial zoonótico, na Amazônia Ocidental.(AU)
Subject(s)
Animals , Rodentia/microbiology , Bacterial Infections and Mycoses/diagnosis , Animals, Wild/microbiology , Trichophyton/pathogenicity , Brazil , Candida/pathogenicity , Microsporum/pathogenicityABSTRACT
Background: Dermatophytes, fungi of universal distribution, invade semi or fully keratinized structures, such as skin, fur/ hair and nails. The various species of dermatophytes are classified into three genera anamorphic: Microsporum, Trichophyton and Epidermophyton. The genus Epidermophyton includes only E. floccosum, that rarely affects animals. The main species responsible for the disease in dogs and cats are Microsporum canis, M. gypseum and Trichophyton mentagrophytes, which were characterized through conventional mycological methodology (microscopic examination with KOH and culture). Molecular methodologies, such as real-time PCR, can contribute to a rapid laboratory diagnosis, helping clinicians to initiate an early antifungal treatment. This case report describes a case of canine dermatophytosis due to Trichophyton mentagrophytes detected from a clinical sample by SYBR-Green real-time PCR. Case: A 8-year-old dog, rescued from the street, was referred to a private veterinary clinic in the city of Canoas, RS, Brazil, presenting generalized lymphadenomegaly, crusted lesions all over the body, generalized alopecia, signs of excoriation and epistaxis. Initially, were administered prednisone [1 mg/kg every 48 h, BID] and cephalexin [30 mg/kg, BID]. Weekly baths with benzoyl peroxide were also given. The therapy was not clinically successful. Wood's Lamp Test was negative. As a differential diagnosis, PCR for detection of Leishmania was negative. Complete blood count and serum biochemical assay were also performed. For mycological diagnosis, hair specimen was clarified and examined microscopically using 10% potassium hydroxide (KOH) for the visualization of chains of arthroconidia (ectothrix invasion of hair). The infected hair was plated onto MycoselTM Agar, incubated at 28°C for 15 days. Microscopy of hyphae/ conidia and macroscopic colony characteristics (colors and texture) were conducted for the differentiation of the species within the genus Microsporum and Trichophyton. In addition, real-time PCR was applied for direct analysis of the fungal DNA obtained from the hair sample. Microscopic examination was negative. The dermatophyte present in the hair sample was confirmed as Trichophyton mentagrophytes by culture and qPCR (melting-point analysis). The patient was treated with systemic itraconazole [10 mg/ kg SID - 90 days]. Twice-weekly application of 2.5 % miconazole and 2% chlorhexidine shampoo until complete cure. Discussion: Dermatophytosis is often listed as self-limiting infection; however, animal dermatophytosis can spread between pets, as well as a zoonotic transmission to humans. The literature on dermatophytosis indicates that Microsporum canis is the predominant etiological agent, followed by M. gypseum. Trichophyon mentagrophytes that appear in a lower percentage of isolation. The culture of hair, even with specific medium containing chloramphenicol and cyclohexamide, may present contaminating fungi, not related to dermatophytosis, which can inhibit or override the growth of dermatophytes. The use of real-time PCR provided a faster and specific diagnosis of dermatophytosis when compared to the conventional mycological methodology for detection and identification of T. mentagrophytes, which takes around 10 to 15 days for culture. It is possible to use this technique as an alternative diagnosis for dermatophytes associated to clinical hair samples of dogs.
Subject(s)
Animals , Male , Dogs , Tinea/veterinary , Trichophyton/isolation & purification , Dermatomycoses/diagnosis , Dermatomycoses/veterinary , Molecular Diagnostic Techniques/veterinary , Real-Time Polymerase Chain Reaction/veterinaryABSTRACT
Trichophyton violaceum es un dermatofito antropofílico endémico en África, Europa, Centroamérica y China. El incremento de los fenómenos de movilidad humana ha contribuido a su aparición en áreas no endémicas. Su principal manifestación clínica es la tinea capitis, seguida por la tinea corporis. En la población pediátrica afecta con mayor frecuencia el cuero cabelludo; y en adultos, la piel glabra. Presentamos el primer caso en Chile de tinea causada por T violaceum. Correspondió a una mujer chilena de 21 años que presentó placas faciales de un mes de evolución después de un viaje a Tanzania, África, sin respuesta a tratamientos médicos previos. Se sospechó una dermatofitosis alóctona y mediante cultivos especiales, se identificó una colonia de crecimiento lento, coloración violeta-negruzca, superficie cerosa y rugosa, con vellosidades aterciopeladas; compatible con T violaceum. Se confirmó mediante secuenciación de ADN ribosomal amplificando la región ITS. Se trató con terbinafina oral con respuesta clínica completa.
Trichophyton violaceum is an anthropophilic dermatophyte endemic in Africa, Europe, Central America and China. The increase in human mobility has recently contributed to the appearance in non-endemic areas. The main clinical manifestation is tinea capitis followed by tinea corporis. We present the first case in Chile of tinea caused by T violaceum. The case was a 21 year-old Chilean woman who presented asymptomatic facial plaques one month after arriving from Tanzania, Africa, with no clinical response to previous medical treatments. An allochthonous dermatophytosis was suspected and with special cultures, a slow-growing colony was identified with a violet-blackish color, waxy and rough surface, and velvety villi; all characteristics of T violaceum. The diagnosis was confirmed by ribosomal DNA sequencing amplifying the ITS region. She was treated with oral terbinafine obtaining a complete clinical response.
Subject(s)
Humans , Female , Young Adult , Tinea/diagnosis , Tinea/drug therapy , Trichophyton/isolation & purification , Trichophyton/genetics , Chile , Terbinafine/therapeutic use , Antifungal Agents/therapeutic useABSTRACT
Dermatophytosis is the most common human skin infection worldwide caused by dermatophytes, such as Trichophyton interdigitale and Trichophyton rubrum. Itraconazole (ITZ) is one of the main antifungals used to treat these infections. However, especially for onychomycosis, the treatment requires long-term regimens, increasing the possibility of drug resistance. We evaluated the effects of ITZ in the physiology, virulence, and interaction of T. interdigitale with phagocytes and mice cutaneous infection. In a screening test, fungal growth in the presence of ITZ led to the spontaneous selection of less susceptible T. interdigitale and T. rubrum strains. Interestingly, this phenotype was permanent for some T. interdigitale strains. Then, we studied three T. interdigitale strains: one susceptible and two ITZ-adapted. The ITZ-adapted strains were also less susceptible to the cell wall and membrane stressors, suggesting a multidrug resistance (MDR) phenotype associated with the increased ERG11 and MDR3 expression. These strains also presented substantial alterations in ergosterol content, lipid peroxidation, biofilm, and extracellular matrix production. During interaction with macrophages, ITZ-adapted strains were less engulfed but increased the intracellular oxidative and nitrosative bursts. In addition, ITZ-adapted strains presented a reduced ability to grow in a murine model of dermatophytosis, although causing the same tissue damage as the parental strain. In conclusion, the T. interdigitale ITZ adaptation increases tolerance to antifungals and alters the interaction with macrophages and a mammalian host. We hypothesized that successive exposure to ITZ may influence the emergence of adapted strains and lead to the recalcitrance of dermatophytosis.
Subject(s)
Arthrodermataceae , Rodent Diseases , Tinea , Humans , Mice , Animals , Itraconazole/pharmacology , Itraconazole/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Trichophyton , Tinea/microbiology , Tinea/veterinary , Virulence , Microbial Sensitivity Tests/veterinary , MammalsABSTRACT
La tiña capitis (TC) es una micosis superficial del cuero cabelludo, considerada una de las infecciones más frecuentes por dermatofitos en niños. Hasta la actualidad, las especies descritas con mayor frecuencia en nuestro medio son el Microsporum y, en segundo término, Trichophyton, los cuales se contraen principalmente por contacto directo con animales o seres humanos infectados, respectivamente. Se presenta el caso de una paciente de 8 años con alopecia y lesiones inflamatorias de 2 años de evolución, en la que finalmente se llegó al diagnóstico de TC inflamatoria causada por T. tonsurans, un hongo antropofílico considerado poco frecuente en Argentina y emergente en la provincia de Buenos Aires. Este patógeno presenta alta transmisibilidad; son varios los países que han reportado brotes escolares y comunitarios. Se debe resaltar la importancia de su sospecha clínica temprana para un tratamiento adecuado.
Tinea capitis (TC) is a superficial mycosis of the scalp, considered one of the most common dermatophyte infections in children. Until now, the species mainly described in our environment are Microsporum and secondly Trichophyton, which are contracted mainly by direct contact with infected animals or humans, respectively. We present the case of an 8-year-old patient with alopecia and inflammatory lesions of 2 years of evolution, finally reaching the diagnosis of inflammatory tinea capitis caused by T. tonsurans, an anthropophilic fungus considered rare in Argentina and emerging in the province of Buenos Aires. This pathogen has high transmissibility; several countries have reported school and community outbreaks. The importance of its early clinical suspicion for adequate treatment should be emphasized.