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Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese AntifungalâResistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.
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Antifúngicos , Consenso , Farmacorresistencia Fúngica , Tiña , Humanos , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , China , Tiña/tratamiento farmacológico , Tiña/microbiología , Tiña/diagnóstico , Trichophyton/efectos de los fármacos , Trichophyton/aislamiento & purificaciónRESUMEN
Dermatophytic disease is a rare condition, primarily described in North Africa. This orphan disease owes its name to Hadida and Schousboe. Although the pathophysiology remains poorly understood, it is often associated with immune deficiency and occurs in the context of high consanguinity, as in our case. We report the case of a 24-year-old man who presented a trichophytic disease due to Trichophyton rubrum, admitted for the appearance of numerous subcutaneous nodules, prompting consultation at our institution. This dermatophytic disease typically begins with recurrent ringworm of the scalp or involvement of hairless skin. The dermatophytes involved are of anthropophilic and zoophilic origin, with T. violaceum being the most frequently isolated species in ringworm cases in the Maghreb. To date, no treatment regimen has been established. However, improving immune status and using antifungals have delayed or prevented the visceral dissemination of the disease.
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The failure to successfully treat dermatophyte-related diseases is often due to the formation of biofilms, which makes dermatophytes resistant to antifungals. Here, an attempt has been made to assess inhibition of dermatophyte biofilm production using photodynamic therapy and rhamnolipid biosurfactant. Two methods were used to inhibit biofilm formation by dermophytes Trichophyton mentagrophytes, Trichophyton rubrum and Trichophyton verrucosum, Microsporum canis and Microsporum gypseum. The first method was the use of rhamnolipid with concentrations of 39 to 1000 ppm and the second was the use of photodynamic method with concentrations of 8, 16 and 32 µg/ml of methylene blue. In addition, these two methods were evaluated simultaneously. The biofilm formation was evaluated using spectrophotometry and scanning electron microscopy. Biosurfactant has been shown to have an improved ability to inhibit the formation of biofilm by the strains. Although photodynamic therapy has not been successful, but in combination with biosurfactant, it may have a synergistic effect. By investigating the effect of rhamnolipid on the formation of biofilm, it was found that Microsporum species has a relatively stronger attachment to the surfaces of the wells compared to trichophyton species. The biofilms were evaluated with electron microscope in the simultaneous treatment of rhamnolipid and photodynamics. The results showed that after the treatment, the biofilms became discrete and their structural integrity was reduced. Even in Microsporum species, which were among the most resistant dermatophytes, the changes in the fungal biofilm after treatment were significant.
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Background: Dermatophytosis is a fungal infection that targets the skin and its appendages, such as the nails and hair. It affects all age groups and is estimated to affect approximately 20-25% of the population across the world. There are insufficient data on the clinic-mycological pattern of dermatophytosis in Odisha, a coastal state in eastern India. The study aims to explore the clinico-mycological pattern of prevailing superficial cutaneous fungal infections and to identify the specific species as per the site of skin involvement. Methods: This is a cross-sectional study conducted in the Department of Dermatology in collaboration with the Department of Microbiology at a tertiary health care centre, Odisha, for a period of 2 years, from October 2020 to September 2022. Participants aged 18-65 years with active dermatophyte infections of the skin were included in the study. Clinical examination and mycological workup were performed, and the collected samples were divided into two parts, one for direct microscopy and the other for fungal culture. Results: According to our study, the most common isolate was Trichophyton mentagrophytes (21.7%), followed by T. rubrum (11.7%), and 5.3% of cultures showed T. schoenleinii isolates, whereas Microsporum canis and Microsporum gypseum constituted 2.7% and 0.7%, respectively. Conclusion: The present study focuses on the prevalence and clinical trends of different dermatophyte species associated with dermatophytosis in eastern India. Due to the favourable climate of Odisha, superficial mycoses are prevalent here, and according to our study, Trichophyton mentagrophytes is the predominate isolate in this region.
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A 42-year-old Vietnamese egg factory worker in Ishikawa prefecture, Japan, presented with itchy concentric erythema on the trunk and left calf. The lesions tested positive by direct potassium hydroxide examination, and two fungal strains were isolated. The isolates produced conidia abundantly and were morphologically indistinguishable from Trichophyton mentagrophytes/interdigitale, but were identified as Trichophyton indotineae by internal transcribed spacer sequence of ribosomal DNA. The lesions were refractory to treatment with topical luliconazole (LLCZ) cream for 4 weeks but subsided with oral itraconazole (ITCZ) 100 mg/day for 4 weeks in combination with topical lanoconazole (LCZ) cream. The lesions recurred 6 weeks after discontinuation of oral ITCZ, and an additional isolate was cultured. The minimum inhibitory concentrations of antimycotics for the isolate cultured at the first visit were: terbinafine (TBF) 0.03 µg/mL, ITCZ 0.015 µg/mL, LLCZ 0.0005 µg/mL, and LCZ 0.002 µg/mL. No TBF-resistant mutation in the amino acid sequence of squalene epoxidase, i.e., Leu 393 Ser/Phe or Phe 397 Leu, was detected in the isolate. The reason for recalcitrance in this case, despite the isolate's sensitivity to antimycotics, was unclear. Possible factors include insufficient use of the antimycotics, incomplete removal of abundantly produced conidia from the lesions, the patient's environment, and a language gap between the patient and physician hindering communication.
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Increasing resistance of dermatophytes against antifungals creates global public health problems, rendering essential a better understanding of virulence mechanisms and factors determining host-specificity of dermatophytes. Since dermatophytes switch from a saprophytic to a parasitic lifestyle by reprogramming gene expression, reliable experimental models are needed to investigate the pathogenesis of dermatophytosis. Here, a relevant mouse model of Trichophyton benhamiae dermatophytosis was assessed, together with a model based on reconstructed human epidermis (RHE), allowing their respective validation regarding fungal gene expressed during infection. The use of a standardized inoculum induced a natural-like superficial infection in mice. The severity and persistence of lesions enabled the assessment of infection markers, including mouse-specific pro-inflammatory molecules and fungal genes previously reported as potential virulence factors. Upregulated expression of fungal genes, including those encoding subtilisins, in infected RHE revealed that dermatophytes deploy similar processes as those observed during in vivo infection. The RHE model was then used to compare infections by anthropophilic Trichophyton rubrum and zoophilic T. benhamiae. Therefore, these two models represent complementary analytical tools to study the pathogenesis of acute dermatophytoses. In addition, we have identified certain fungal markers of infection and highlighted the existence of different mechanisms deployed by zoophilic versus anthropophilic dermatophytes.
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INTRODUCTION: There is an increasing number of reports of Trichophyton indotineae infections. This species is usually poorly responsive to terbinafine. AREAS COVERED: A literature search was conducted in May 2024. T.indotineae infections detected outside the Indian subcontinent are generally associated with international travel. Reports of local spread are mounting.As a newly identified dermatophyte species closely related to the T. mentagrophytes complex with limited genetic and phenotypic differences, there is an unmet need to develop molecular diagnosis for T. indotineae. Terbinafine has become less effective as a first-line agent attributed to mutations in the squalene epoxidase gene (Leu393Phe, Phe397Leu). Alternative therapies include itraconazole for a longer time-period or a higher dose (200 mg/day or higher). Generally, fluconazole and griseofulvin are not effective. In some cases, especially when the area of involvement is relatively small, topical non-allylamine antifungals may be an option either as monotherapy or in combination with oral therapy. In instances when the patient relapses after apparent clinical cure then itraconazole may be considered. Good antifungal stewardship should be considered at all times. EXPERT OPINION: When both terbinafine and itraconazole are ineffective, options include off-label triazoles (voriconazole and posaconazole). We present four patients responding to these newer triazoles.
Ringworm (dermatophytosis, tinea) is a fungal infection of the skin, hair and nails that is commonly seen by primary and secondary healthcare providers. An estimated 2025% of the global population is affected by this condition. In Europe and the United States, tineas are often treated empirically using over-the-counter medications, which can increase the risk of resistance development.While antifungal resistance is not a new problem, this topic has garnered the attention of physicians and researchers in recent years due to an outbreak from South Asia caused by a new pathogen known as Trichophyton indotineae. In this review, we summarize the global prevalence, diagnosis methods, antifungal resistance profile and treatment options for T. indotineae. Currently, most cases outside of South Asia are linked to international travel, there is evidence suggesting local person-to-person transmission and transmission via animal contact. One hurdle to surveilling the spread of this pathogen is the requirement of complex molecular diagnosis, tackling this challenge will require the development of newer assays.Terbinafine, a widely available antifungal drug, is becoming less effective owing to resistance mutations of the squalene epoxidase gene. Itraconazole has shown effectiveness, especially with a higher dose and a longer treatment duration. There is a significant risk of T. indotineae infections becoming chronic with episodes of relapse. When both terbinafine and itraconazole fail, newer agents such as posaconazole and voriconazole can be considered. Combination therapy using oral and topical medications should also be considered.
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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].
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BACKGROUND: Trichophyton (T.) erinacei is a rare but emerging zoonotic dermatophyte that is rarely isolated as a human pathogen, with only a few cases extensively described in the literature. PATIENTS AND METHODS: We conducted a systematic search to identify eligible articles reporting demographics, clinical characteristics, and the therapeutic approach regarding T. erinacei infection in humans. RESULTS: 168 patients affected by T. erinacei were reported in the international literature between inception and November 2023. Only 56 cases (32.1%) were fully described. The median age at diagnosis was 26 years, the female/male ratio was around 2:1. The main source of the disease was the hedgehog. The infection presented with a combination of erythema, scaly plaques, pustules, papules, vesicles, oedema, and erosion; the most common locations were the hands and the head. The most frequently conducted examination was fungal culture, but gene sequencing and mass spectrometry improved both speed and precision in the most recent diagnostic course. Topical clotrimazole and systemic terbinafine were the most chosen treatment. CONCLUSIONS: Trichophyton erinacei should be considered in patients with erythematous scaly patches and recent contact with hedgehogs. Terbinafine should be considered as a first-line effective treatment, griseofulvin and azoles could be considered valid alternatives.
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Background Dermatophytosis is a superficial fungal infection caused by a group of pathogenic keratinophilic fungi. The increase in the incidence of superficial fungal infections, combined with the emergence of antifungal resistance, represents both a global health challenge and a considerable economic burden. Recent years have witnessed a surge in dermatophytosis cases, accompanied by the emergence of antifungal-resistant strains. This study aimed to analyze the in vitro antifungal susceptibility patterns and determine the minimum inhibitory concentrations (MIC) of antifungal drugs among isolated species using the broth microdilution method. Methodology This cross-sectional study was conducted between September 2021 and August 2022. Patients with symptoms or clinical features of fungal infection, including skin, hair, and nail lesions indicative of Tinea infections, were included. Samples underwent processing, including potassium hydroxide (KOH) mounting, direct microscopic examination, and culture on Sabouraud Dextrose Agar (SDA) with antibiotics. Antifungal susceptibility testing was subsequently conducted. Results Trichophyton mentagrophytes emerged as the most common isolate among patients with Tinea infections. MIC values of various drugs were analyzed, with itraconazole exhibiting a minimum MIC of 0.03 µg/ml and a maximum of 0.50 µg/ml. Terbinafine showed an MIC of 0.010 µg/ml and a maximum of 1.00 µg/ml. Ketoconazole had a minimum MIC of 0.03 µg/ml and a maximum of 0.50 µg/ml. Fluconazole exhibited a minimum MIC of 0.10 µg/ml and a maximum of 1.00 µg/ml. Lastly, miconazole demonstrated a minimum MIC of 0.03 µg/ml and a maximum of 2.00 µg/ml. Conclusion Accurate diagnosis is crucial for fungal infections to enable early treatment and reduce transmission. With an increasing trend in resistance among dermatophytes, there is a growing need to conduct susceptibility testing of antifungal agents, particularly in cases of long-term infections, recurrent infections, and individuals who do not respond to medication.
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Caffeine affords several beneficial effects on human health, acting as an antioxidant, anti-inflammatory agent, and analgesic. Caffeine is widely used in cosmetics, but its antimicrobial activity has been scarcely explored, namely against skin infection agents. Dermatophytes are the most common fungal agents of human infection, mainly of skin infections. This work describes the in vitro effect of caffeine during keratinocyte infection by Trichophyton mentagrophytes, one of the most common dermatophytes. The results show that caffeine was endowed with antidermatophytic activity with a MIC, determined following the EUCAST standards, of 8 mM. Caffeine triggered a modification of the levels of two major components of the fungal cell wall, ß-(1,3)-glucan and chitin. Caffeine also disturbed the ultrastructure of the fungal cells, particularly the cell wall surface and mitochondria, and autophagic-like structures were observed. During dermatophyte-human keratinocyte interactions, caffeine prevented the loss of viability of keratinocytes and delayed spore germination. Overall, this indicates that caffeine can act as a therapeutic and prophylactic agent for dermatophytosis.
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Antifúngicos , Arthrodermataceae , Cafeína , Queratinocitos , Cafeína/farmacología , Queratinocitos/efectos de los fármacos , Queratinocitos/microbiología , Humanos , Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Pared Celular/efectos de los fármacos , Tiña/tratamiento farmacológico , Tiña/microbiología , Quitina/farmacología , Quitina/químicaRESUMEN
Tinea cruris, a dermatophyte fungal infection predominantly caused by Trichophyton rubrum and Epidermophyton floccosum, primarily affects the groin, pubic region, and adjacent thigh. Its recurrence is frequent, attributable to repeated fungal infections in susceptible individuals, especially those with onychomycosis or tinea pedis, which act as reservoirs for dermatophytes. Given the persistent nature of tinea cruris, vaccination emerges as a promising strategy for fungal infection management, offering targeted, durable protection against various fungal species. Vaccines stimulate both humoral and cell-mediated immunity and are administered prophylactically to prevent infections while minimizing the risk of antifungal resistance development. Developing fungal vaccines is challenging due to the thick fungal cell wall, similarities between fungal and human cells, antigenic variation, and evolutionary resemblance to animals, complicating non-toxic target identification and T-cell response variability. No prior research has shown an mRNA vaccine for T. rubrum. Hence, this study proposes a novel mRNA-based vaccine for tinea cruris, potentially offering long-term immunity and reducing reliance on antifungal medications. This study explores the complete proteome of T. rubrum, identifying potential protein candidates for vaccine development through reverse vaccinology. Immunogenic epitopes from these candidates were mapped and integrated into multitope vaccines and reverse translated to construct mRNA vaccines. Then, the mRNA was translated and computationally assessed for physicochemical, chemical, and immunological attributes. Notably, 1,3-beta-glucanosyltransferase, CFEM domain-containing protein, cell wall galactomannoprotein, and LysM domain-containing protein emerged as promising vaccine targets. Antigenic, immunogenic, non-toxic, and non-allergenic cytotoxic T lymphocyte, helper T lymphocyte, and B lymphocyte epitopes were selected and linked with appropriate linkers and Toll-like receptor (TLR) agonist adjuvants to formulate vaccine candidates targeting T. rubrum. The protein-based vaccines underwent reverse translation to construct the mRNA vaccines, which, after inoculation, were translated again by host ribosomes to work as potential components for triggering the immune response. After that, molecular docking, normal mode analysis, and molecular dynamic simulation confirmed strong binding affinities and stable complexes between vaccines and TLR receptors. Furthermore, immune simulations of vaccines with and without adjuvant demonstrated activation of immune responses, evidenced by elevated levels of IgG1, IgG2, IgM antibodies, cytokines, and interleukins. There was no significant change in antibody production between vaccines with and without adjuvants, but adjuvants are crucial for activating the innate immune response via TLRs. Although mRNA vaccines hold promise against fungal infections, further research is essential to assess their safety and efficacy. Experimental validation is crucial for evaluating their immunogenicity, effectiveness, and safety.
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Antifungal-resistant dermatophyte infections have recently emerged as a global public health concern. A survey of US infectious diseases specialists found that only 65% had heard of this issue and just 39% knew how to obtain testing to determine resistance. Increased clinician awareness and access to testing for antifungal-resistant dermatophytosis are needed.
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Antifúngicos , Farmacorresistencia Fúngica , Tiña , Humanos , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Estados Unidos/epidemiología , Tiña/microbiología , Tiña/epidemiología , Tiña/tratamiento farmacológico , Encuestas y Cuestionarios , Arthrodermataceae/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
The Trichophyton mentagrophytes complex comprises a group of dermatophyte fungi responsible for various dermatological infections. The increasing drug resistance of this species complex, especially terbinafine resistance of Trichophyton indotineae, is a major concern in dermatologist practice. This study provides a comprehensive analysis of T. mentagrophytes complex strains isolated from patients in Hue City, Vietnam, focusing on their phenotypic and genetic characteristics, antifungal susceptibility profiles, and molecular epidemiology. Keratinophilic fungi from dermatophytosis culture samples were identified morphologically and phenotypically, with species and genotypes confirmed by internal transcribed spacer sequencing and phylogenetic analysis. Antifungal susceptibility testing was carried out to evaluate their susceptibility to itraconazole, voriconazole, and terbinafine. The 24% (n = 27/114) of superficial mycoses were phenotypically attributed to T. mentagrophytes complex isolates. Trichophyton interdigitale, mainly genotype II*, was predominant (44.4%), followed by T. mentagrophytes genotype III* (22.2%), T. indotineae (14.8%), T. tonsurans (11.2%), and T. mentagrophytes (7.4%). While all isolates were susceptible to itraconazole and voriconazole, half of T. indotineae isolates exhibited resistance to terbinafine, linked to the Phe397Leu mutation in the SQLE protein. This study highlighted the presence of terbinafine-resistant T. indotineae isolates in Vietnam, emphasizing the need to investigate dermatophyte drug resistance and implement effective measures in clinical practice.
Species diversity within the Trichophyton mentagrophytes complex isolated from dermatophytosis in Hue City, Vietnam, was observed. Terbinafine-resistant T. indotineae isolates were detected for the first time in Vietnam, emphasizing the importance of implementing antifungal susceptibility testing to effectively manage and prevent the spread of resistant isolates.
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Antifúngicos , Farmacorresistencia Fúngica , Genotipo , Pruebas de Sensibilidad Microbiana , Filogenia , Terbinafina , Tiña , Humanos , Vietnam , Antifúngicos/farmacología , Terbinafina/farmacología , Tiña/microbiología , Arthrodermataceae/efectos de los fármacos , Arthrodermataceae/genética , Arthrodermataceae/clasificación , Arthrodermataceae/aislamiento & purificación , Masculino , Análisis de Secuencia de ADN , Itraconazol/farmacología , ADN Espaciador Ribosómico/genética , Femenino , Persona de Mediana Edad , ADN de Hongos/genética , Epidemiología Molecular , Adulto , TrichophytonRESUMEN
BACKGROUND: Dermatophytosis is a common skin infection of cats and many other animals. A reliable diagnosis is crucial because of the zoonotic potential of dermatophytes. The routine mycological diagnostic procedures for dermatophytosis are widely known, but in the case of some isolates, identification based on phenotypic characteristics may be incorrect. Infections caused by Chrysosporium spp. are usually described in reptiles, but in other animals they are uncommon. CASE PRESENTATION: This study presents a description of a cat with dermatological lesions, that was mistakenly diagnosed with Trichophyton spp. dermatophytosis. Clinical material for mycological examination was collected from alopecic areas on the back of the neck, the ventral abdomen, and the hindlimbs. The initial identification based on phenotypic properties indicated Trichophyton spp. The result of the MALDI-ToF MS allowed the exclusion of the Trichophyton genus. Ultimately, the correct identification as Chrysosporium articulatum was obtained based on the sequencing of ribosomal genes. CONCLUSIONS: Interpretation of the results of the mycological examination of samples collected from animals' skin or hair shafts is always challenging. Thus, careful consideration of the primary cause of the clinical lesions observed on the skin is mandatory, and the culture results are worth supporting by molecular methods.
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Enfermedades de los Gatos , Chrysosporium , Tiña , Trichophyton , Gatos , Animales , Enfermedades de los Gatos/microbiología , Enfermedades de los Gatos/diagnóstico , Tiña/veterinaria , Tiña/diagnóstico , Tiña/microbiología , Chrysosporium/aislamiento & purificación , Chrysosporium/genética , Trichophyton/aislamiento & purificación , Diagnóstico Diferencial , Masculino , Dermatomicosis/veterinaria , Dermatomicosis/diagnóstico , Dermatomicosis/microbiologíaRESUMEN
Fungi, such as Trichophyton rubrum (T. rubrum) and Microsporum canis Bodin Anamorph (M. canis Bodin Anamorph) are the main pathogens of dermatophysis. According to ancient books records, Rumex japonicus Houtt. (RJH) has a miraculous effect on the treatment of dermatophysis. To reveal the anti-fungi (T. rubrum and M. canis Bodin Anamorph) components and its mechanism of the Rumex japonicus Houtt. The vinegar extraction and alcohol precipitation, HPLC and nuclear magnetic resonance spectroscopy (NMR) were employed for analyzing the chemical compositions of RJH; in vitro anti-fungal experiment was investigated including test the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC), spore germination rate, nucleic acid, protein leakage rate, biofilm structure, and the mechanism of anti-fungal and anti-fungal biofilms in RJH. Seven anthraquinones and their glycoside compounds were obtained in this study respectively, such as chrysophanol, physcion, aloe-emodin, emodin, rhein, emodin-8-O-ß-D-glucoside and chrysophanol-8-O-ß-D-glucoside. In vitro anti-fungal experiment results showed that RJH extracts have good anti-fungal activity for dermatophytic fungi. Among them, the MIC of the rhein, emodin and aloe-emodin against T. rubrum are 1.9 µg/ml, 3.9 µg/ml and 15.6 µg/ml, respectively; the MIC of emodin and aloe-emodin against M. canis Bodin Anamorph are 7.8 µg/ml and 62.5 µg/ml, respectively. In addition, its active components can inhibit fungal spore germination and the formation of bud tube, change cell membrane permeability, prevent hyphal growth, destroy biofilm structure, and down-regulate the expression of agglutinin-like sequence family 1 of the adhesion phase of biofilm growth. The study shows that RJH play a fungicidal role.
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Antraquinonas , Antifúngicos , Biopelículas , Glicósidos , Pruebas de Sensibilidad Microbiana , Microsporum , Rumex , Antraquinonas/farmacología , Antraquinonas/química , Antraquinonas/aislamiento & purificación , Rumex/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Glicósidos/farmacología , Glicósidos/química , Microsporum/efectos de los fármacos , Biopelículas/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Emodina/farmacología , Emodina/química , Emodina/análogos & derivados , ArthrodermataceaeRESUMEN
Trichophyton rubrum is one of the most frequently isolated fungi in patients with dermatophytosis. Despite its clinical significance, the molecular mechanisms of drug resistance and pathogenicity of T. rubrum remain to be elucidated because of the lack of genetic tools, such as efficient gene targeting systems. In this study, we generated a T. rubrum strain that lacks the nonhomologous end-joining-related gene ku80 (Δku80) and then developed a highly efficient genetic recombination system with gene targeting efficiency that was 46 times higher than that using the wild-type strain. Cyp51A and Cyp51B are 14-α-lanosterol demethylase isozymes in T. rubrum that promote ergosterol biosynthesis and are the targets of azole antifungal drugs. The expression of cyp51A mRNA was induced by the addition of the azole antifungal drug efinaconazole, whereas no such induction was detected for cyp51B, suggesting that Cyp51A functions as an azole-responsive Cyp51 isozyme. To explore the contribution of Cyp51A to susceptibility to azole drugs, the neomycin phosphotransferase (nptII) gene cassette was inserted into the cyp51A 3'-untranslated region of Δku80 to destabilize the mRNA of cyp51A. In this mutant, the induction of cyp51A mRNA expression by efinaconazole was diminished. The minimum inhibitory concentration for several azole drugs of this strain was reduced, suggesting that dermatophyte Cyp51A contributes to the tolerance for azole drugs. These findings suggest that an efficient gene targeting system using Δku80 in T. rubrum is applicable for analyzing genes encoding drug targets.
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Onychomycosis, a fungal nail infection, is primarily caused by dermatophytes, yeasts, and non-dermatophyte moulds (NDMs). The incidence of this disease and the predominance of specific pathogens vary across different regions and evolve. This study aimed to elucidate the epidemiology of onychomycosis and the pattern of causative pathogens in Beijing, and to ascertain the in vitro antifungal susceptibility profiles of Trichophyton rubrum against itraconazole (ITR), terbinafine (TER), and fluconazole (FLU). Involving 245 patients of onychomycosis with positive fungal culture results, the study implemented internal transcribed spacer (ITS) sequencing of ribosomal DNA (rDNA) on all collected samples. The mean age of the participants was 37.93 ± 13.73 years, with a male-to-female ratio of 1.53:1. The prevalence of toenail infections was significantly higher than that of fingernails. Distal and lateral subungual onychomycosis (DLSO) were the most frequent clinical classifications. PCR results indicated that dermatophytes were the most prevalent pathogens, followed by yeasts and NDMs, among which T. rubrum was the most dominant dermatophyte. TER demonstrated high sensitivity to T. rubrum. However, in clinical settings, some patients with onychomycosis exhibit a poor response to TER treatment. The relationship between in vitro antifungal sensitivity and clinical effectiveness is complex, and understanding the link between in vitro MIC values and clinical efficacy requires further investigation.