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1.
Mycopathologia ; 189(4): 59, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890181

RESUMO

Dermatophyte biofilms frequently count for inadequate responses and resistance to standard antifungal treatments, resulting in refractory chronic onychomycosis infection. Although antimicrobial photodynamic therapy (aPDT) has clinically proven to exert significant antifungal effects or even capable of eradicating dermatophyte biofilms, considerably less is known about the molecular mechanisms underlying aPDT and the potential dysregulation of signaling networks that could antagonize its action. The aim of this study is to elucidate the molecular mechanisms underlining aPDT combat against dermatophyte biofilm in recalcitrant onychomycosis and to decipher the potential detoxification processes elicited by aPDT, facilitating the development of more effective photodynamic interventions. We applied genome-wide comparative transcriptome analysis to investigate how aPDT disrupting onychomycosis biofilm formed by three distinct dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, the most frequently occurring pathogenic species. In total, 352.13 Gb of clean data were obtained for the transcriptomes of dermatophyte biofilms with or without aPDT treatment, resulting in 2,422.42 million reads with GC content of 51.84%, covering 99.9%, 98.5% and 99.4% of annotated genes of T. rubrum, T. mentagrophytes, and M. gypseum, respectively. The genome-wide orthologous analysis identified 6624 transcribed single-copy orthologous genes in all three species, and 36.5%, 6.8% and 17.9% of which were differentially expressed following aPDT treatment. Integrative orthology analysis demonstrated the upregulation of oxidoreductase activities is a highly conserved detoxification signaling alteration in response to aPDT across all investigated dermatophyte biofilms. This study provided new insights into the molecular mechanisms underneath anti-dermatophyte biofilm effects of aPDT and successfully identified a conserved detoxification regulation upon the aPDT application.


Assuntos
Arthrodermataceae , Biofilmes , Perfilação da Expressão Gênica , Fotoquimioterapia , Biofilmes/efeitos dos fármacos , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/genética , Microsporum/efeitos dos fármacos , Microsporum/genética , Humanos , Antifúngicos/farmacologia , Onicomicose/microbiologia , Onicomicose/tratamento farmacológico , Transcriptoma
2.
Clin Lab ; 70(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38868878

RESUMO

BACKGROUND: Onychomycosis is a chronic nail infection, and dermatophytes, yeasts, and nondermatophytic molds may be the causative agents. This study aimed to determine the etiological agents of onychomycosis by using conventional and molecular methods. METHODS: Between June 2020 and July 2021, 37 patients with a presumptive diagnosis of onychomycosis and mycological evidence (culture and/or EUROArray Dermatomycosis assay) were included in the study. Organisms detected in cultured nail specimens were identified by combined phenotypic characteristics and by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). An EUROarray Dermatomycosis assay was used for molecular detection of fungal pathogens. RESULTS: The EUROArray Dermatomycosis assay was positive for a single fungal target in 23 samples, and 14 samples were positive by culture. The most common pathogen was Trichophyton rubrum in both methods. Coinfection was detected in 14 samples by using molecular methods, and Trichophyton rubrum and Fusarium solani (9 samples) were the most common pathogens detected together. Trichophyton spp., nondermatophyte molds, and Candida spp. were detected in 33 (89.2%), 16 (43.2%), and 6 (16.2%) samples, respectively, when the two methods were evaluated together. CONCLUSIONS: Our results revealed that fungal culture allows the diagnosis of onychomycosis, but it is not as sensitive as the EUROArray Dermatomycosis test, especially in patients receiving antifungal therapy.


Assuntos
Arthrodermataceae , Onicomicose , Humanos , Onicomicose/microbiologia , Onicomicose/diagnóstico , Feminino , Arthrodermataceae/isolamento & purificação , Arthrodermataceae/genética , Masculino , Turquia/epidemiologia , Adulto , Pessoa de Meia-Idade , Idoso , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adulto Jovem , Adolescente , Trichophyton/isolamento & purificação , Trichophyton/genética , Técnicas de Diagnóstico Molecular/métodos , Coinfecção/microbiologia , Coinfecção/diagnóstico , Coinfecção/epidemiologia
3.
Mycopathologia ; 189(4): 52, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864945

RESUMO

Treatment-resistant dermatophytosis caused by the members of the Trichophyton mentagrophytes/Trichophyton interdigitale species group (TMTISG) is increasing worldwide. We aimed to determine the prevalence of TMTISG in patients with dermatophytosis in two centers from north of Iran and detect the possible mutations in the squalene epoxidase (SQLE) gene in relevant terbinafine (TRB) resistant pathogenic isolates. From November 2021 to December 2022, 1960 patients suspected to dermatophytosis and referred to two mycology referral laboratories in the north of Iran were included in the study. Identification of all dermatophyte isolates was confirmed by RFLP of rDNA internal transcribed spacer (ITS) regions. Antifungal susceptibility testing against five common antifungals using the CLSI-M38-A3 protocol was performed. The TMTISG isolates resistant to TRB, were further analyzed to determine the possible mutations in the SQLE gene. Totally, 647 cases (33%) were positive for dermatophytosis of which 280 cases (43.3%) were identified as members of TMTISG. These were more frequently isolated from tinea corporis 131 (44.56%) and tinea cruris 116 (39.46%). Of 280 TMTISG isolates, 40 (14.3%) were resistant to TRB (MIC ≥ 4 µg/mL), all found to be T. indotineae in ITS sequencing. In SQLE sequencing 34 (85%) of TRB-resistant isolates had coincident mutations of Phe397Leu and Ala448Thr whereas four and two isolates had single mutations of Phe397Leu and Leu393Ser, respectively. Overall, the resistance of Iranian TMTISG isolates to TRB greatly occurred by a mutation of Phe397Leu in the SQLE gene as alone or in combination with Ala448Thr. Nevertheless, for the occurrence of in vitro resistance, only the presence of Phe397Leu mutation seems to be decisive.


Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Esqualeno Mono-Oxigenase , Terbinafina , Tinha , Irã (Geográfico)/epidemiologia , Farmacorresistência Fúngica/genética , Humanos , Antifúngicos/farmacologia , Terbinafina/farmacologia , Estudos Transversais , Tinha/microbiologia , Tinha/epidemiologia , Prevalência , Arthrodermataceae/genética , Arthrodermataceae/efeitos dos fármacos , Masculino , Feminino , Esqualeno Mono-Oxigenase/genética , Adulto , Pessoa de Meia-Idade , Mutação , Idoso , Adulto Jovem , Adolescente , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Criança
4.
Mycopathologia ; 189(4): 51, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864977

RESUMO

Data on the epidemiology of tinea capitis (TC), an infection of the scalp by dermatophytes, are scarce in Cameroon. This study aimed to determine the prevalence of TC among school-children in the Dschang Subdivision, Western Cameroon. A cross-sectional study was carried out in June 2021 in Dschang including pupils aged 5-13. First, a standardized questionnaire was administered to participant for the collection of sociodemographic data. Then, samples were collected and cultured onto Sabouraud-Chloramphenicol-Gentamicin Agar. The etiological agents were identified based on their morphological features and with MALDI-TOF mass spectrometry. A total of 1070 children were clinically examined and 108 (10.1%) children presented with TC lesions. The mean age of the 1070 participants was 8.3 ± 2.6 years (range: 5-13 years); 772 (72.2%) were males. The use of borehole water (OR = 0.01, 95%CI[0.001-0.03]), spring water (OR = 0.2, 95%CI[0.08-0.50]), rainwater (OR = 0.004, 95%CI[0.001-0.016]), and hairdressing salons visits (OR = 0.413, 95%CI[0.196-0.872]) were associated with a decreased TC risk in the multivariate logistic regression analysis. In contrast, sharing bed with siblings (OR = 4.48, 95%CI[2.095-9.60]) was associated with an increased TC risk in children. Among the 32 dermatophytes isolated in culture, Microsporum audouinii was the most frequent (43.8%), followed by Trichophyton rubrum (25.0%) and T. soudanense (25.0%). Microsporum canis and T. violaceum were both rarely isolated. Further studies are warranted to assess the association of TC with domestic water usage that has been highlighted in this study.


Assuntos
Tinha do Couro Cabeludo , Tinha do Couro Cabeludo/epidemiologia , Tinha do Couro Cabeludo/microbiologia , Humanos , Camarões/epidemiologia , Criança , Masculino , Feminino , Adolescente , Estudos Transversais , Pré-Escolar , Prevalência , Inquéritos e Questionários , Microsporum/isolamento & purificação , Fatores de Risco , Arthrodermataceae/isolamento & purificação , Arthrodermataceae/classificação , Instituições Acadêmicas , Trichophyton/isolamento & purificação
5.
Sci Rep ; 14(1): 12669, 2024 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830918

RESUMO

Dermatophytes show a wide geographic distribution and are the main causative agents of skin fungal infections in many regions of the world. Recently, their resistance to antifungal drugs has led to an obstacle to effective treatment. To address the lack of dermatophytosis data in Iraq, this study was designed to investigate the distribution and prevalence of dermatophytes in the human population and single point mutations in squalene epoxidase gene (SQLE) of terbinafine resistant isolates. The identification of 102 dermatophytes isolated from clinical human dermatophytosis was performed through morphological and microscopic characteristics followed by molecular analysis based on ITS and TEF-1α sequencing. Phylogeny was achieved through RAxML analysis. CLSI M38-A2 protocol was used to assess antifungal susceptibility of the isolates to four major antifungal drugs. Additionally, the presence of point mutations in SQLE gene, which are responsible for terbinafine resistance was investigated. Tinea corporis was the most prevalent clinical manifestation accounting for 37.24% of examined cases of dermatophytosis. Based on ITS, T. indotineae (50.98%), T. mentagrophytes (19.61%), and M. canis (29.41%) was identified as an etiologic species. T. indotineae and T. mentagrophytes strains were identified as T. interdigitale based on TEF-1α. Terbinafine showed the highest efficacy among the tested antifungal drugs. T. indotineae and T. mentagrophytes showed the highest resistance to antifungal drugs with MICs of 2-4 and 4 µg/mL, while M. canis was the most susceptible species. Three of T. indotineae isolates showed mutations in SQLE gene Phe397Leu substitution. A non-previously described point mutation, Phe311Leu was identified in T. indotineae and mutations Lys276Asn, Phe397Leu and Leu419Phe were diagnosed in T. mentagrophytes XVII. The results of mutation analysis showed that Phe397Leu was a destabilizing mutation; protein stability has decreased with variations in pH, and point mutations affected the interatomic interaction, resulting in bond disruption. These results could help to control the progression of disease effectively and make decisions regarding the selection of appropriate drugs for dermatophyte infections.


Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Mutação Puntual , Esqualeno Mono-Oxigenase , Tinha , Humanos , Antifúngicos/farmacologia , Iraque/epidemiologia , Tinha/microbiologia , Tinha/epidemiologia , Tinha/tratamento farmacológico , Farmacorresistência Fúngica/genética , Masculino , Arthrodermataceae/genética , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/patogenicidade , Arthrodermataceae/isolamento & purificação , Feminino , Esqualeno Mono-Oxigenase/genética , Adulto , Filogenia , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Criança , Proteínas Fúngicas/genética , Idoso
6.
Mycoses ; 67(6): e13755, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888369

RESUMO

BACKGROUND: Tinea faciei, a specific dermatophytosis that affects the glabrous skin of the face, not only causes physical discomfort but also leads to greater psychological distress. Tinea faciei is a public health concern. OBJECTIVES: To analyse the epidemiological characteristics, responsible dermatophyte species and clinical features of tinea faciei in Hangzhou. METHODS: Data were obtained from the Laboratory Information System of the Mycology Laboratory and Medical Information System at a hospital in Hangzhou. Isolates were identified based on their macroscopic appearance and microscopic morphology. RESULTS: Tinea faciei was diagnosed in 701 patients, involving 359 males and 342 females, aged between 2 months and 97 years. In total, 499 isolates (71.18%) were identified as Trichophyton rubrum. Anthropophilic isolates were identified in 297 (82.73%) males and 207 (60.53%) females (p < .01). Among patients with anthropophilic dermatophytes infection, 447 (88.69%) were adults. Zoophilic dermatophytes were isolated in 57 (15.88%) males and 130 (38.01%) females (p < .01), among whom 108 (57.75%) were children. CONCLUSIONS: Anthropophilic dermatophytes, especially T. rubrum, were the predominant cause of tinea faciei, while zoophilic dermatophytes were the most prevalent in children. Compared with men, women may be more susceptible to zoophilic dermatophytes.


Assuntos
Arthrodermataceae , Tinha , Humanos , Masculino , Feminino , Adolescente , China/epidemiologia , Criança , Tinha/microbiologia , Tinha/epidemiologia , Adulto , Pessoa de Meia-Idade , Pré-Escolar , Adulto Jovem , Lactente , Idoso , Arthrodermataceae/isolamento & purificação , Arthrodermataceae/classificação , Idoso de 80 Anos ou mais , Dermatoses Faciais/microbiologia , Dermatoses Faciais/epidemiologia , Dermatoses Faciais/patologia , Face/microbiologia , Face/patologia , Inquéritos e Questionários
8.
Mycoses ; 67(6): e13754, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38880935

RESUMO

BACKGROUND: Tinea faciei is a relatively uncommon dermatophyte infection. The studies, which included clinical forms, and isolated species of dermatophytes, are limited. MATERIALS AND METHODS: This retrospective study aims to determine the causative organism, clinical characteristics, treatments and outcomes of patients with tinea faciei attending the dermatologic clinic, Siriraj Hospital, from 1 January 2017 to 30 September 2021. Demographic data, clinical presentations, isolated dermatophyte species, treatments and outcomes were collected and analysed. RESULTS: A total of 151 tinea faciei cases were observed. Trichophyton rubrum (48.6%), Trichophyton mentagrophytes complex (22.2%) and Microsporum canis (18.1%) were common causative agents. Tinea faciei was commonly detected in females (64.9%) with a history of pets (54.6%). Clinical presentations often involved plaques and scales on the cheeks. Among patients with lesions on the cheek, mycological cure was observed significantly less often compared to those without cheek lesions. Patients with other concurrent skin or nail infections, a history of topical steroids and a history of previous fungal infection had a slightly longer duration of mycological cure than those without factors. Recurrent infection was found in 33.3%. Male, history of previous fungal infection, and lesions on the cheeks were significantly associated with recurrent infection. CONCLUSIONS: Fungal infection of the face was commonly found in women and patients with pets. The most common pathogen that caused tinea faciei was T. rubrum. Topical antifungal treatments could be used with favourable outcomes. The history of past infection and lesion on the cheeks should be carefully assessed to be vigilant for recurrent infection.


Assuntos
Antifúngicos , Arthrodermataceae , Microsporum , Tinha , Humanos , Estudos Retrospectivos , Feminino , Masculino , Tinha/microbiologia , Tinha/tratamento farmacológico , Tinha/epidemiologia , Tailândia/epidemiologia , Adulto , Antifúngicos/uso terapêutico , Pessoa de Meia-Idade , Arthrodermataceae/isolamento & purificação , Arthrodermataceae/classificação , Arthrodermataceae/efeitos dos fármacos , Adulto Jovem , Adolescente , Microsporum/isolamento & purificação , Criança , Resultado do Tratamento , Idoso , Dermatoses Faciais/microbiologia , Dermatoses Faciais/tratamento farmacológico , Pré-Escolar
10.
Expert Rev Anti Infect Ther ; 22(6): 399-412, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38841996

RESUMO

INTRODUCTION: Terbinafine is considered the gold standard for treating skin fungal infections and onychomycosis. However, recent reports suggest that dermatophytes are developing resistance to terbinafine and the other traditional antifungal agents, itraconazole and fluconazole. When there is resistance to terbinafine, itraconazole or fluconazole, or when these agents cannot used, for example, due to potential drug interactions with the patient's current medications, clinicians may need to consider off-label use of new generation azoles, such as voriconazole, posaconazole, fosravuconazole, or oteseconazole. It is essential to emphasize that we do not advocate the use of newer generation azoles unless traditional agents such as terbinafine, itraconazole, or fluconazole have been thoroughly evaluated as first-line therapies. AREAS COVERED: This article reviews the clinical evidence, safety, dosage regimens, pharmacokinetics, and management algorithm of new-generation azole antifungals. EXPERT OPINION: Antifungal stewardship should be the top priority when prescribing new-generation azoles. First-line antifungal therapy is terbinafine and itraconazole. Fluconazole is a consideration but is generally less effective and its use may be off-label in many countries. For difficult-to-treat skin fungal infections and onychomycosis, that have failed terbinafine, itraconazole and fluconazole, we propose consideration of off-label voriconazole or posaconazole.


Assuntos
Antifúngicos , Azóis , Farmacorresistência Fúngica , Onicomicose , Humanos , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/farmacologia , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Azóis/administração & dosagem , Azóis/farmacologia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Uso Off-Label , Interações Medicamentosas , Arthrodermataceae/efeitos dos fármacos
11.
Mycopathologia ; 189(3): 37, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704808

RESUMO

Trichophyton rubrum is a human fungal pathogen that causes dermatophytosis, an infection that affects keratinized tissues. Integrated molecular signals coordinate mechanisms that control pathogenicity. Transcriptional regulation is a core regulation of relevant fungal processes. Previous RNA sequencing data revealed that the absence of the transcription factor StuA resulted in the differential expression of the MAPK-related high glycerol osmolarity gene (hog1) in T. rubrum. Here we validated the role of StuA in regulating the transcript levels of hog1. We showed through RT-qPCR that transcriptional regulation controls hog1 levels in response to glucose, keratin, and co-culture with human keratinocytes. In addition, we also detected hog1 pre-mRNA transcripts that underwent alternative splicing, presenting intron retention in a StuA-dependent mechanism. Our findings suggest that StuA and alternative splicing simultaneously, but not dependently, coordinate hog1 transcript levels in T. rubrum. As a means of preventing and treating dermatophytosis, our results contribute to the search for new potential drug therapies based on the molecular aspects of signaling pathways in T. rubrum.


Assuntos
Processamento Alternativo , Arthrodermataceae , Regulação Fúngica da Expressão Gênica , Proteínas Quinases Ativadas por Mitógeno , Tinha , Fatores de Transcrição , Humanos , Arthrodermataceae/genética , Arthrodermataceae/metabolismo , Glucose/metabolismo , Queratinócitos/microbiologia , Queratinas/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tinha/metabolismo , Tinha/microbiologia
12.
Pak J Pharm Sci ; 37(2): 257-263, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38767092

RESUMO

The objective of this study was to identify the major compounds present in Cedar tar obtained by distillation of Cedrus atlantica wood from the Taza forest (Morocco) and to evaluate its antidermatophytic activity in vitro against the three strains of dermatophytes most widespread in Morocco, considered the main prevailing causes of fungal infections of the skin, hair and nails. GC/MS analysis revealed that cedar tar is composed mainly of hydrocarbon sesquiterpenes and oxygenated sesquiterpenes, with nine major compounds identified, including α-Cedrene, ß-Cadinene, γ-Cadinene, ß-Himachelene, α-Turmerone, ß-Turmerone, Ar-tumerone, α-Atlantone and Himachalol. The evaluation of antifungal activity was carried out by the micro dilution technique. The MIC values found were 100µg/mL, 2µg/mL and 0.1µg/mL on Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum canis strains respectively. The observed strong antifungal activity of cedar tar is attributed to the prevalence of oxygenated and hydrocarbon sesquiterpenes, known for their established antidermatophytic properties. This study highlights the potential of the Atlas Cedar tar as an effective antifungal agent for the treatment of superficial mycoses, particularly dermatophytoses.


Assuntos
Antifúngicos , Arthrodermataceae , Cedrus , Testes de Sensibilidade Microbiana , Microsporum , Microsporum/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/isolamento & purificação , Arthrodermataceae/efeitos dos fármacos , Cedrus/química , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Cromatografia Gasosa-Espectrometria de Massas , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Marrocos
13.
J Ethnopharmacol ; 331: 118344, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754641

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dermatophytes are notorious pathogens capable of infecting various mammals skin, posing serious threats to human health and overall life quality worldwide. Artemisia argyi has been recorded and applied for over a thousand years to treat skin itching. Although it has the potential to be developed as a plant-based antifungal agent, it's antifungal activity and action mechanism of active ingredients are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the chemical composition, antifungal activity against skin fungi, and potential mechanisms of Artemisia argyi essential oil (AEO). MATERIALS AND METHODS: The chemical composition of AEO was analyzed by gas chromatography-mass spectrometry (GC-MS) firstly. Flat growth restraint and double half dilution tests was performed to evaluate AEO antifungal activity against Microsporum gypseum, Trichophyton mentagrophytes, and Trichophyton rubrum. And then, the physiological mechanism of AEO inhibiting dermatophytes was systematically explored through scanning electron microscopy, relative conductivity, membrane leakage, ROS content, and antioxidant enzyme activity. Finally, the main pathways were screened through transcriptome sequencing, while the related genes expression levels and enzyme activity were validated. RESULTS: Monoterpenes and sesquiterpenoids were the most highly representative class of AEO. AEO had powerful antifungal activity against M. gypseum, T. mentagrophytes, and T. rubrum, with minimum inhibitory concentration (MIC) values of 0.6, 1.2, and 1.2 µL/mL, respectively. Moreover, AEO can also damage the cell membrane integrity of T. mentagrophytes, resulting in cellular extravasation of intracellular substances. Transcriptome analysis revealed that the main target of AEO is to inhibit electron transfer and oxidative phosphorylation during respiration, ultimately leading to obstruction of normal ATP synthesis and energy metabolism in mitochondria. And a large amount of ROS will generate due to the incompletely catalysis of oxygen under mitochondrial complexes. Coupled with the decrease of antioxidant enzyme (SOD, POD) activity, excessive accumulation of ROS will cause serious oxidative damage to cells and eventually exhibiting antifungal activity against dermatophytes. CONCLUSIONS: The present study demonstrated that Artemisia argyi was a valuable source of active compounds with antifungal activity. These findings support AEO as a potential agent to inhibit dermatophytes and prevent related dermatophytoses.


Assuntos
Antifúngicos , Artemisia , Arthrodermataceae , Óleos Voláteis , Fosforilação Oxidativa , Estresse Oxidativo , Artemisia/química , Antifúngicos/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Arthrodermataceae/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Cromatografia Gasosa-Espectrometria de Massas
14.
Acta Trop ; 255: 107237, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723739

RESUMO

The surge in domestic cat adoption across India, particularly the rising preference for high-pedigree cats, coupled with environmental factors, has resulted in increased incidence of dermatophytosis among feline companions. Despite this growing concern, there is a noticeable scarcity of studies in India delving into the etiological factors contributing to dermatophytosis in cats. This disease is a threat to animal health and carries public health significance, given that cats are recognized reservoir hosts for Microsporum canis, a common dermatophyte affecting humans and animals. This study endeavours to identify the dermatophytes affecting cats and establish a standardized therapeutic regimen while accounting for the local stigma surrounding the regular bathing of cats. The study involved the examination of 82 cats presenting dermatological lesions, when subjected to cultural examination in dermatophyte test medium revealed 36 afflicted with dermatophytes. Isolates were presumptively identified by staining using lactophenol cotton blue, Chicago sky blue 6B, and Calcofluor white stains. Molecular-level identification of the isolates was confirmed through PCR-RFLP, amplifying the Internal Transcribed Spacer Sequence of 16 s rDNA, followed by restriction digestion using the Mva1 enzyme. Among the thirty-six isolates, 29 were identified as M. canis, while the remaining 7 were M. gypseum. The cases were categorized into five groups and treated with Lime Sulphur dip, 4 % chlorhexidine shampoo, a shampoo containing 2 % miconazole and 4 % chlorhexidine, oral itraconazole alone, and a combination of oral itraconazole with lime-Sulphur dip. Statistical analysis revealed that the response was notably swifter with lime Sulphur dip when considering only topical therapy. Moreover, the mycological cure was most expeditious when combining Lime Sulphur dip with oral itraconazole. These findings underscore the pivotal role of topical biocides in feline dermatophytosis treatment, potentially reducing the reliance on specific antifungals and thereby contributing to the mitigation of antimicrobial resistance emergence.


Assuntos
Antifúngicos , Doenças do Gato , Microsporum , Tinha , Gatos/microbiologia , Animais , Doenças do Gato/microbiologia , Doenças do Gato/tratamento farmacológico , Índia/epidemiologia , Tinha/veterinária , Tinha/microbiologia , Tinha/tratamento farmacológico , Tinha/epidemiologia , Antifúngicos/uso terapêutico , Microsporum/isolamento & purificação , Microsporum/genética , Masculino , Feminino , Arthrodermataceae/isolamento & purificação , Arthrodermataceae/genética , Arthrodermataceae/classificação , Arthrodermataceae/efeitos dos fármacos , Itraconazol/uso terapêutico , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética
15.
Antimicrob Agents Chemother ; 68(5): e0160923, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38567956

RESUMO

The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. Trichophyton rubrum is the most commonly isolated fungus in dermatophytosis. In T. rubrum, we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast Saccharomyces cerevisiae polyamine transport kinase 2 (Ptk2), and found that T. rubrum Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both T. rubrum and S. cerevisiae, Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in S. cerevisiae. Overexpression of T. rubrum Pma1 (TrPma1) in T. rubrum Ptk2 knockout strain (ΔTrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes.


Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Saccharomyces cerevisiae , Terbinafina , Terbinafina/farmacologia , Antifúngicos/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Farmacorresistência Fúngica/genética , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fosforilação
16.
Expert Opin Pharmacother ; 25(5): 511-519, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38623728

RESUMO

INTRODUCTION: The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention. AREAS COVERED: This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was T. mentagrophytes. However, T. indotineae emerged as the most prevalent isolate with mutations in the SQLE gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole.Overall, the most prevalent SQLE mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent). EXPERT OPINION: Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of SQLE mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered.


Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Mutação , Terbinafina , Tinha , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Humanos , Farmacorresistência Fúngica/genética , Tinha/tratamento farmacológico , Tinha/microbiologia , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/genética , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia
17.
Eur Rev Med Pharmacol Sci ; 28(6): 2144-2154, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567576

RESUMO

OBJECTIVE: A large number of patients applying to the dermatology clinics are affected by fungal diseases, and a significant portion of which are superficial fungal infections. Dermatophyte infections are a notable public health concern and frequently encountered in clinical practice. Dermatophytosis not only compromises the quality of life but also predisposes individuals to various comorbidities due to its role as a gateway for secondary bacterial agents. This study aims to determine the species distribution of dermatophytes prevalent and assess their susceptibility to antifungal drugs. PATIENTS AND METHODS: Skin, nail, and hair samples were obtained from patients with a clinical diagnosis of dermatophytosis. Samples were all cultured to isolate and identify the species. In vitro liquid microdilution tests were conducted to assess the susceptibility of the isolated strains against terbinafine, fluconazole, griseofulvin, and butenafine. RESULTS: A total of 353 samples were obtained from the hair, skin, and nail lesions of 326 patients. Dermatophyte was isolated in 71 of the samples (20.1%). The cultured dermatophyte subtypes included Trichophyton rubrum (13.8% in 49 samples), Microsporum audouini (5.7% in 20 samples), and Trichophyton mentagrophytes (0.6% in 2 samples). Antifungal susceptibility testing revealed that terbinafine was the most effective antifungal drug against all dermatophyte species, while fluconazole exhibited the highest resistance. CONCLUSIONS: The most common dermatophytosis agent in our region is T. rubrum. The least antifungal resistance was found against terbinafine. Conducting antifungal susceptibility tests is crucial for selecting effective treatment regimens and early detection of resistance development.


Assuntos
Arthrodermataceae , Tinha , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Turquia/epidemiologia , Mar Negro , Qualidade de Vida , Trichophyton , Testes de Sensibilidade Microbiana , Tinha/tratamento farmacológico , Tinha/microbiologia
18.
Braz J Microbiol ; 55(2): 1287-1295, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453819

RESUMO

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.


Assuntos
Antifúngicos , Arthrodermataceae , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Timol , Triazóis , Antifúngicos/farmacologia , Antifúngicos/química , Triazóis/farmacologia , Triazóis/química , Humanos , Timol/farmacologia , Timol/química , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/genética , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Queratinócitos/efeitos dos fármacos , Trichophyton/efeitos dos fármacos , Trichophyton/genética
19.
Mycoses ; 67(3): e13713, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483066

RESUMO

BACKGROUND: Dermatophytosis is an intractable superficial mycosis in humans and animals mainly caused by Trichophyton mentagrophytes (T. mentagrophytes), with a global prevalence of about 20%. Keratinocytes are the most abundant participants in skin immunity, and they also play a role in the first-line defence against T. mentagrophytes. However, no studies of keratinocyte responses against T. mentagrophytes infection based on the whole transcriptome have been reported. OBJECTIVES: Here, we systematically analysed changes in keratinocytes infected with T. mentagrophytes using whole transcriptome sequencing technology. METHODS: The phenotypic changes in keratinocytes after infection with 1 × 105 conidia/mL T. mentagrophytes were observed by light microscopy, scanning electron microscopy, transmission electron microscopy and terminal deoxynucleotidyl transferase dUTP nick end labeling. RNA-sequencing (RNA-seq), small RNA-seq technology and related bioinformatics methods were used to systematically analyse the whole transcriptome changes in keratinocytes upon T. mentagrophytes stimulation. RESULTS: We found that T. mentagrophytes infection caused morphological changes, membrane damage, the formation of irregular organelles and keratinocyte apoptosis. A total of 204 differentially expressed (DE) circular RNAs (circRNAs), 868 DE long noncoding RNAs (lncRNAs), 2973 DE mRNAs and 209 DE micro RNAs (miRNAs) were identified between noninfected and T. mentagrophytes-infected keratinocytes. The expression level of selected RNAs was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Functional enrichment analysis revealed that the parental genes of DE circRNAs were related to cell response, cell death and establishment of the skin barrier. Genes targeted by miRNA were involved in regulating the initiation of the immune response. Based on the expression level of circRNAs, lncRNAs, mRNAs and miRNAs, circRNA-miRNA-mRNA competing endogenous (ceRNA) networks comprised of 159 DE miRNAs, 141 DE circRNAs and 2307 DE mRNAs, and lncRNA-miRNA-mRNA ceRNA networks comprised of 790 DE lncRNAs, 190 DE miRNAs and 2663 DE mRNAs were constructed. The reliability of two selected ceRNA networks was verified using qRT-PCR. Further functional enrichment analysis revealed that the DE mRNAs interacting with circRNAs and lncRNAs in the ceRNA network mainly participated in fungal recognition, inflammation, the innate immune response and the death of keratinocytes. CONCLUSIONS: Our findings might provide new evidence on the pathogenesis of T. mentagrophytes-induced dermatophytosis, which is essential for identifying new therapeutic targets for dermatophytosis treatment.


Assuntos
Arthrodermataceae , MicroRNAs , RNA Longo não Codificante , Tinha , Animais , Humanos , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Reprodutibilidade dos Testes , Perfilação da Expressão Gênica , MicroRNAs/genética , RNA Mensageiro/genética , Queratinócitos/metabolismo
20.
Mycopathologia ; 189(2): 29, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483637

RESUMO

The emerging pathogen Trichophyton indotineae, often resistant to terbinafine (TRB), is known to cause severe dermatophytoses such as tinea corporis and tinea cruris. In order to achieve successful treatment for these infections, insight in the resistance profile of T. indotineae strains and rapid, reliable identification is necessary. In this research, a screening medium was tested on T. indotineae strains (n = 20) as an indication tool of TRB resistance. The obtained results were confirmed by antifungal susceptibility testing (AST) for TRB following the in vitro broth microdilution reference method. Additionally, AST was performed for eight other antifungal drugs: fluconazole, itraconazole, voriconazole, ketoconazole, griseofulvin, ciclopirox olamine, naftifine and amorolfine. Forty-five percent of the strains were confirmed to be resistant to terbinafine. The TRB resistant strains showed elevated minimal inhibitory concentration values for naftifine and amorolfine as well. DNA sequencing of the squalene epoxidase-encoding gene showed that TRB resistance was a consequence of missense point mutations in this gene, which led to amino acid substitutions F397L or L393F. MALDI-TOF MS was used as a quick, accurate identification tool for T. indotineae, as it can be challenging to distinguish it from closely related species such as Trichophyton mentagrophytes or Trichophyton interdigitale using morphological characteristics. While MALDI-TOF MS could reliably identify ≥ 95% of the T. indotineae strains (depending on the spectral library), it could not be used to successfully distinguish TRB susceptible from TRB resistant strains.


Assuntos
Alilamina/análogos & derivados , Antifúngicos , Arthrodermataceae , Terbinafina/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Trichophyton/genética , Arthrodermataceae/genética , Testes de Sensibilidade Microbiana , Farmacorresistência Fúngica/genética
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