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1.
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
2.
Arch Argent Pediatr ; 122(6): e202310254, 2024 12 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38608007

RESUMO

Tinea capitis is a dermatophytosis, which is more common in children. It is caused by dermatophytes that vary according to the region; the most frequently isolated dermatophyte in our setting is Microsporum canis. Given its anthropophilic nature, its dissemination via interpersonal transmission and through the use of hair care tools is very common. In the course of the past year, an increase has been reported in the incidence of a pathogen that was very rare in our setting: Trichophyton tonsurans. Here we describe a retrospective study of cases of tinea capitis caused by Trichophyton tonsurans identified between September 2021 and March 2023 in the Department of Pediatric Dermatology at a general hospital of the City of Buenos Aires.


La tinea capitis es una dermatofitosis, más frecuente en niños. Está causada por hongos dermatofitos que varían según la región; el más frecuentemente aislado en nuestro medio es el Microsporum canis. Dado su carácter antropofílico, la transmisión por vía interpersonal y mediante el uso de instrumentos de cuidado capilar es muy habitual. En el transcurso del último año, se ha reportado un incremento en la incidencia de un patógeno que era muy poco habitual en nuestro medio: el Trichophyton tonsurans. Presentamos un estudio retrospectivo de los casos de tinea capitis por Trichophyton tonsurans identificados en el período comprendido entre septiembre de 2021 y marzo de 2023 en la Sección de Dermatología Infantil de un hospital general de la Ciudad Autónoma de Buenos Aires.


Assuntos
Tinha do Couro Cabeludo , Tinha do Couro Cabeludo/microbiologia , Tinha do Couro Cabeludo/epidemiologia , Tinha do Couro Cabeludo/diagnóstico , Humanos , Argentina/epidemiologia , Estudos Retrospectivos , Criança , Masculino , Feminino , Pré-Escolar , Adolescente , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Lactente , Arthrodermataceae/isolamento & purificação
3.
Lett Appl Microbiol ; 77(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38499446

RESUMO

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 1.9‒62.5 to 15.6‒62.5 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.


Assuntos
Arthrodermataceae , Curcumina , Curcumina/análogos & derivados , Antifúngicos/farmacologia , Candida , Curcumina/farmacologia , Testes de Sensibilidade Microbiana , Ergosterol , Trichophyton
4.
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
5.
Microorganisms ; 12(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38258017

RESUMO

Dermatophytes associated with bacteria can lead to severe, difficult-to-treat infections and contribute to chronic infections. Trichophyton rubrum, Staphylococcus aureus, and Staphylococcus epidermidis can form biofilms influenced by nutrient availability. This study investigated biofilm formation by these species by utilizing diverse culture media and different time points. These biofilms were studied through scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), biomass, metabolic activity, and colony-forming units (CFUs). The results revealed that mixed biofilms exhibited high biomass and metabolic activity when cultivated in the brain heart infusion (BHI) medium. Both bacterial species formed mature biofilms with T. rubrum within 72 h, irrespective of media. The timing of bacterial inoculation was pivotal in influencing biomass and metabolic activity. T. rubrum's development within mixed biofilms depended on bacterial addition timing, while pre-adhesion influenced fungal growth. Bacterial communities prevailed initially, while fungi dominated later in the mixed biofilms. CLSM revealed 363 µm thick T. rubrum biofilms with septate, well-developed hyphae; S. aureus (177 µm) and S. epidermidis (178 µm) biofilms showed primarily cocci. Mixed biofilms matched T. rubrum's thickness when associated with S. epidermidis (369 µm), with few hyphae initially. Understanding T. rubrum and Staphylococcal interactions in biofilms advances antimicrobial resistance and disease progression knowledge.

6.
Pharmaceutics ; 16(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38258083

RESUMO

Topical treatments for onychomycosis are of interest to those seeking to avoid systemic drug interactions and to improve systemic safety. This work aimed to develop aqueous-based, simple, and cost-effective vehicles that provide high solubility for ciclopirox and enable the delivery of an active through channels created by nail microporation. Following solubility tests, aqueous gels and thermogels based on hydroxypropylmethylcellulose and poloxamer 407, respectively, were loaded with 8% and 16% ciclopirox. Their performance was then compared to the marketed lacquer Micolamina® in in vitro release tests with artificial membranes and in in vitro permeation tests with human nail clippings with and without poration. Finally, a microbiological assay compared the best gel formulations and the reference product. Little correlation was observed between the in vitro release and the permeation data, and the drug release was highly membrane-dependent. Ciclopirox nail retention in single-dose, porated nails tests was larger than in daily-dosing, non-porated nail conditions. The series of new gel and thermogel vehicles delivered ciclopirox more effectively than Micolamina® in single-dose, porated nail experiments. The inhibition of Trichophyton rubrum activity was significantly increased with microporated nails when the gel formulations were applied but not with Micolamina®. Overall, the results suggest that the new vehicles could be successfully combined with nail microporation to improve the drug delivery and efficacy of topical antifungal medication while reducing the dosing frequency, facilitating patients' adherence.

7.
J Fungi (Basel) ; 10(1)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38248981

RESUMO

Trichophyton rubrum is the leading causative agent of dermatophytosis worldwide. Keratinocytes are the first line of defense that drives an immune response against fungal invasion. Host-specific pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) to trigger immunological pathways. Fungal cell wall components are the primary sources of fungal PAMPs, and some pathogens increase cell wall rearrangement to evade the immune system. Glycolysis and enhanced lactate levels are critical for improving host immune responses to fungal infections. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), we evaluated the transcriptional responses of human genes involved in fungal recognition and glycolytic metabolism and fungal cell-wall-related genes in a co-culture model of human keratinocytes with T. rubrum. We observed the upregulation of several Toll-like receptors (TLRs), NOD-like receptors (NLRs), and glycolytic genes. Complementarily, we measured intra- and extracellular glucose levels and the increase in lactate production in the co-culture supernatant. We noted a distinct transcriptional regulation pattern of fungal cell-wall-related genes from fungal growth on keratin as the primary carbon source compared to co-culture with human keratinocytes. Our results showed new insights into the transcriptional adaptation of keratinocytes, particularly in regulating genes involved in sensing and metabolic processes, during the interaction with T. rubrum.

8.
Photodiagnosis Photodyn Ther ; 44: 103875, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37923285

RESUMO

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.


Assuntos
Onicomicose , Fotoquimioterapia , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Fotoquimioterapia/métodos , Azóis/farmacologia , Azóis/uso terapêutico , Trichophyton , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Biofilmes
9.
Nat Prod Res ; : 1-9, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37933528

RESUMO

The present study aimed to investigate the antifungal activity of citronellal (CIT) against clinical isolates of T. rubrum and to show the possible mechanism of action involved. The antifungal potential of CIT was evaluated from the Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC) and assays with ergosterol and sorbitol, to elucidate the possible mechanisms of action, and molecular docking. MIC and MFC values ranged from 4 to 512 µg/mL. Regarding the mechanism of action, the monoterpene demonstrated interaction with fungal ergosterol. In addition, it is possible to observe that CIT acts on crucial enzymes for the biosynthesis and maintenance of the fungal cell membrane, due to the ability of the monoterpene to bind to CYP51. The results obtained in this research demonstrate that CIT has the potential to become, in the future, a product for the treatment of dermatophytosis.

10.
Int Microbiol ; 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875749

RESUMO

Onychomycosis is a nail infection caused by dermatophytes, non-dermatophyte fungi, and yeasts, especially Candida species. The present study evaluated the combinatorial effect of different cultured extracts of Candida parapsilosis and Trichophyton mentagrophytes and Trichophyton rubrum with fluconazole, itraconazole, and terbinafine against clinical isolates of Trichophyton rubrum. In addition, investigation of the action of the extracts on the wall or membrane was performed. Pure and mixed cultures of Candida parapsilosis and dermatophytes were filtered through a 0.2-µm membrane and submitted to liquid-liquid extraction using ethyl acetate. After a checkerboard, trial with drugs was performed to evaluate the synergistic interaction with the extract. The results obtained for the minimum inhibitory concentration (MIC) of extracts against the T. rubrum strain in isolation were 500-8000 µg/mL. The MIC range for fluconazole, itraconazole, and terbinafine were 2-32 µg/mL, 0.25-0.5 µg/mL, 0.03-64 µg/mL, respectively. However, when the extract was combined with drugs, the MIC values decreased: extracts 1.9-1000 µg/mL, fluconazole 0.25-4, itraconazole 0.03-0.06 µg/mL, and terbinafine 0.001-0.02 µg/mL. The MIC values of the extracts in the Roswell Park Memorial Institute 1640 medium (RPMI) supplemented with sorbitol did not change, suggesting any action on the cell wall. However, in the presence of RPMI supplemented with ergosterol, MIC values of the extracts increased by up to 2×, indicating action on the fungal cell membrane. A synergistic action was observed between products and drugs, detecting a decrease in MIC values. There is potential and a new therapeutic perspective for fungal control.

12.
Med Mycol Case Rep ; 41: 48-51, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37706043

RESUMO

A case of tinea corporis by Trichophyton indotineae observed in Argentina is presented. The patient had a history of having spent 18 months in Tulum, Mexico. She was suffering from tinea corporis in the anterior region of both thighs and the gluteal area. A mycological study was performed and T. mentagrophytes complex was isolated. The fungus was later identified as T. indotineae by DNA sequencing and treatment with SUBA-itraconazole was initiated with good clinical response.

13.
J Mycol Med ; 33(3): 101412, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37451067

RESUMO

Onychomycosis is the most prevalent nail ailment in adults, accounting for 50% of all nail infections. Dermatophyte fungi are the primary cause, but non-dermatophyte molds (NDM) and yeasts can also cause onychomycosis. It remains important to precisely determine the fungal cause of onychomycosis since the response to current treatments may vary between fungal classes. Real-time polymerase chain reaction (qPCR) has become a widespread tool for detecting fungal organisms for diagnosis due to its sensitivity and ability to detect down to the species level. This retrospective study aims to evaluate the qPCR Onycho+ test for dermatophyte detection using remnants of toenails from a cohort of patients from Puerto Rico.  Two hundred forty-two toenail samples submitted for histological examination via Periodic acid Schiff (PAS) staining for suspected onychomycosis were analyzed by the Onycho+ test and Sanger sequencing of the internal transcribed spacer (ITS-2). Compared to the gold standard Sanger sequencing method, the Onycho+ test reported an agreement of 91.39%, a sensitivity of 100% and a specificity of 84.5% in detecting dermatophytes, superior to the histology method which had a 69.53% agreement, 85.1% sensitivity and 57.1% specificity. The distribution of fungal organisms detected in this cohort shows a dermatophyte majority but a higher-than-expected proportion of NDMs. Nails negative for the Onycho+ test and positive for histology were mostly NDMs. This study demonstrates that the clinical performance of the Onycho+ test is superior to histology in detecting dermatophytes and that a combination of Onycho+ and histology can result in a higher clinical accuracy.


Assuntos
Arthrodermataceae , Onicomicose , Adulto , Humanos , Onicomicose/diagnóstico , Onicomicose/epidemiologia , Onicomicose/microbiologia , Estudos Retrospectivos , Porto Rico/epidemiologia , Unhas/microbiologia , Leveduras , Arthrodermataceae/genética
14.
Braz J Microbiol ; 54(2): 1093-1102, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37145298

RESUMO

Heracleum vicinum Boiss., a perennial plant of Angelica in Umbelliferae, is mainly distributed in Sichuan and Hunan of China. Trichophyton rubrum is a common skin fungus causing dermatophyte. The previous experimental study found that the ethanol extract from Heracleum vicinum Boiss. had excellent anti-Trichophyton rubrum activity, especially the ethanol extract further extracted with petroleum ether and dichloromethane has the best antibacterial effect and has good potential for treating dermatophytes. In this study, Heracleum vicinum Boiss. was extracted with ethanol by microwave-assisted ultrasonic extraction method and isolated with silica gel column to obtain a coumarin compound M1-1 by the guidance of anti-Trichophyton rubrum activity, which was characterized by nuclear magnetic resonance spectroscopy(13C-NMR), hydrogen nuclear magnetic resonance (1H-NMR), Fourier transform infrared spectroscopy (FTIR), high-resolution mass spectrometry (HR-ESI-MS), and ultraviolet (UV) and identified as imperatorin and belonged to coumarins, with the minimum inhibitory concentration (MIC) against Trichophyton rubrum of 12.5 µg/mL. According to the discussion on the inhibitory mechanism of the compound, we found that the compound may exert its inhibitory effect by destroying the mycelial membrane and inhibiting the mycelial growth of Trichophyton rubrum. In a word, imperatorin isolated from Heracleum vicinum Boiss. is expected to be used as an antibacterial agent to treat dermatophytes a potential natural compound against Trichophyton rubrum, and a template for drug development of dermatophytes the future.


Assuntos
Arthrodermataceae , Heracleum , Cumarínicos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Etanol/farmacologia , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana
15.
Med Mycol ; 61(5)2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37120732

RESUMO

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).


Assuntos
Arthrodermataceae , Doenças do Gato , Dermatomicoses , Doenças do Cão , Tinha , Gatos , Animais , Cães , Humanos , Arthrodermataceae/genética , Dermatomicoses/diagnóstico , Dermatomicoses/veterinária , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Doenças do Gato/diagnóstico , Doenças do Cão/diagnóstico , Microsporum/genética , Cabelo , Quitina Sintase/genética , Tinha/veterinária , Trichophyton/genética
16.
Med Mycol Case Rep ; 39: 34-37, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36865767

RESUMO

Trichophyton verrucosum is the most commonly dermatophyte involved in cattle ringworm. This work reported a case of bovine dermatophytosis due to Trichophyton verrucosum detected from the clinical sample by SYBR-Green real-time PCR. The strategy was based on the DNA extraction directly from the infected hair followed by real-time PCR and melting-point analysis. A faster and differential diagnosis was observed when compared to the conventional mycological methodology for detection and identification of Trichophyton verrucosum.

17.
J Fungi (Basel) ; 9(2)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36836389

RESUMO

The dermatophyte Trichophyton rubrum is responsible for most human cutaneous infections. Its treatment is complex, mainly because there are only a few structural classes of fungal inhibitors. Therefore, new strategies addressing these problems are essential. The development of new drugs is time-consuming and expensive. The repositioning of drugs already used in medical practice has emerged as an alternative to discovering new drugs. The antidepressant sertraline (SRT) kills several important fungal pathogens. Accordingly, we investigated the inhibitory mechanism of SRT in T. rubrum to broaden the knowledge of its impact on eukaryotic microorganisms and to assess its potential for future use in dermatophytosis treatments. We performed next-generation sequencing (RNA-seq) to identify the genes responding to SRT at the transcript level. We identified that a major effect of SRT was to alter expression for genes involved in maintaining fungal cell wall and plasma membrane stability, including ergosterol biosynthetic genes. SRT also altered the expression of genes encoding enzymes related to fungal energy metabolism, cellular detoxification, and defense against oxidative stress. Our findings provide insights into a specific molecular network interaction that maintains metabolic stability and is perturbed by SRT, showing potential targets for its strategic use in dermatophytosis.

18.
Int J Mol Sci ; 25(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38203573

RESUMO

Trichophyton rubrum is the primary causative agent of dermatophytosis worldwide. This fungus colonizes keratinized tissues and uses keratin as a nutritional source during infection. In T. rubrum-host interactions, sensing a hostile environment triggers the adaptation of its metabolic machinery to ensure its survival. The glyoxylate cycle has emerged as an alternative metabolic pathway when glucose availability is limited; this enables the conversion of simple carbon compounds into glucose via gluconeogenesis. In this study, we investigated the impact of stuA deletion on the response of glyoxylate cycle enzymes during fungal growth under varying culture conditions in conjunction with post-transcriptional regulation through alternative splicing of the genes encoding these enzymes. We revealed that the ΔstuA mutant downregulated the malate synthase and isocitrate lyase genes in a keratin-containing medium or when co-cultured with human keratinocytes. Alternative splicing of an isocitrate lyase gene yielded a new isoform. Enzymatic activity assays showed specific instances where isocitrate lyase and malate synthase activities were affected in the mutant strain compared to the wild type strain. Taken together, our results indicate a relevant balance in transcriptional regulation that has distinct effects on the enzymatic activities of malate synthase and isocitrate lyase.


Assuntos
Arthrodermataceae , Fatores de Transcrição , Humanos , Isocitrato Liase/genética , Malato Sintase/genética , Gluconeogênese/genética , Processamento Alternativo , Carbono , Glucose , Queratinas , Glioxilatos
19.
Braz. J. Vet. Res. Anim. Sci. (Online) ; 60: e203984, 2023. ilus, tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1518164

RESUMO

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)


Assuntos
Animais , Roedores/microbiologia , Infecções Bacterianas e Micoses/diagnóstico , Animais Selvagens/microbiologia , Trichophyton/patogenicidade , Brasil , Candida/patogenicidade , Microsporum/patogenicidade
20.
Rev. chil. infectol ; Rev. chil. infectol;39(6): 740-745, dic. 2022. ilus
Artigo em Espanhol | LILACS | ID: biblio-1431711

RESUMO

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.


Assuntos
Humanos , Feminino , Adulto Jovem , Tinha/diagnóstico , Tinha/tratamento farmacológico , Trichophyton/isolamento & purificação , Trichophyton/genética , Chile , Terbinafina/uso terapêutico , Antifúngicos/uso terapêutico
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