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2.
Mycoses ; 67(6): e13754, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38880935

ABSTRACT

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.


Subject(s)
Antifungal Agents , Arthrodermataceae , Microsporum , Tinea , Humans , Retrospective Studies , Female , Male , Tinea/microbiology , Tinea/drug therapy , Tinea/epidemiology , Thailand/epidemiology , Adult , Antifungal Agents/therapeutic use , Middle Aged , Arthrodermataceae/isolation & purification , Arthrodermataceae/classification , Arthrodermataceae/drug effects , Young Adult , Adolescent , Microsporum/isolation & purification , Child , Treatment Outcome , Aged , Facial Dermatoses/microbiology , Facial Dermatoses/drug therapy , Child, Preschool
3.
Mycoses ; 67(6): e13755, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888369

ABSTRACT

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.


Subject(s)
Arthrodermataceae , Tinea , Humans , Male , Female , Adolescent , China/epidemiology , Child , Tinea/microbiology , Tinea/epidemiology , Adult , Middle Aged , Child, Preschool , Young Adult , Infant , Aged , Arthrodermataceae/isolation & purification , Arthrodermataceae/classification , Aged, 80 and over , Facial Dermatoses/microbiology , Facial Dermatoses/epidemiology , Facial Dermatoses/pathology , Face/microbiology , Face/pathology , Surveys and Questionnaires
4.
Mycopathologia ; 189(4): 52, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864945

ABSTRACT

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.


Subject(s)
Antifungal Agents , Arthrodermataceae , Drug Resistance, Fungal , Microbial Sensitivity Tests , Squalene Monooxygenase , Terbinafine , Tinea , Iran/epidemiology , Drug Resistance, Fungal/genetics , Humans , Antifungal Agents/pharmacology , Terbinafine/pharmacology , Cross-Sectional Studies , Tinea/microbiology , Tinea/epidemiology , Prevalence , Arthrodermataceae/genetics , Arthrodermataceae/drug effects , Male , Female , Squalene Monooxygenase/genetics , Adult , Middle Aged , Mutation , Aged , Young Adult , Adolescent , DNA, Fungal/genetics , DNA, Ribosomal Spacer/genetics , Child
5.
Mycopathologia ; 189(4): 51, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864977

ABSTRACT

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.


Subject(s)
Tinea Capitis , Tinea Capitis/epidemiology , Tinea Capitis/microbiology , Humans , Cameroon/epidemiology , Child , Male , Female , Adolescent , Cross-Sectional Studies , Child, Preschool , Prevalence , Surveys and Questionnaires , Microsporum/isolation & purification , Risk Factors , Arthrodermataceae/isolation & purification , Arthrodermataceae/classification , Schools , Trichophyton/isolation & purification
6.
Sci Rep ; 14(1): 12669, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830918

ABSTRACT

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.


Subject(s)
Antifungal Agents , Arthrodermataceae , Drug Resistance, Fungal , Microbial Sensitivity Tests , Point Mutation , Squalene Monooxygenase , Tinea , Humans , Antifungal Agents/pharmacology , Iraq/epidemiology , Tinea/microbiology , Tinea/epidemiology , Tinea/drug therapy , Drug Resistance, Fungal/genetics , Male , Arthrodermataceae/genetics , Arthrodermataceae/drug effects , Arthrodermataceae/pathogenicity , Arthrodermataceae/isolation & purification , Female , Squalene Monooxygenase/genetics , Adult , Phylogeny , Terbinafine/pharmacology , Terbinafine/therapeutic use , Middle Aged , Adolescent , Young Adult , Child , Fungal Proteins/genetics , Aged
7.
mSphere ; 9(6): e0024824, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38837382

ABSTRACT

Superficial infections of the skin, hair, and nails by fungal dermatophytes are the most prevalent of human mycoses, and many infections are refractory to treatment. As current treatment options are limited, recent research has explored drug synergy with azoles for dermatophytoses. Bisphosphonates, which are approved to treat osteoporosis, can synergistically enhance the activity of azoles in diverse yeast pathogens but their activity has not been explored in dermatophytes or other molds. Market bisphosphonates risedronate, alendronate, and zoledronate (ZOL) were evaluated for antifungal efficacy and synergy with three azole antifungals: fluconazole (FLC), itraconazole (ITR), and ketoconazole (KET). ZOL was the most active bisphosphonate tested, displaying moderate activity against nine dermatophyte species (MIC range 64-256 µg/mL), and was synergistic with KET in eight of these species. ZOL was also able to synergistically improve the anti-biofilm activity of KET and combining KET and ZOL prevented the development of antifungal resistance. Rescue assays in Trichophyton rubrum revealed that the inhibitory effects of ZOL alone and in combination with KET were due to the inhibition of squalene synthesis. Fluorescence microscopy using membrane- and ROS-sensitive probes demonstrated that ZOL and KET:ZOL compromised membrane structure and induced oxidative stress. Antifungal activity and synergy between bisphosphonates and azoles were also observed in other clinically relevant molds, including species of Aspergillus and Mucor. These findings indicate that repurposing bisphosphonates as antifungals is a promising strategy for revitalising certain azoles as topical antifungals, and that this combination could be fast-tracked for investigation in clinical trials. IMPORTANCE: Fungal infections of the skin, hair, and nails, generally grouped together as "tineas" are the most prevalent infectious diseases globally. These infections, caused by fungal species known as dermatophytes, are generally superficial, but can in some cases become aggressive. They are also notoriously difficult to resolve, with few effective treatments and rising levels of drug resistance. Here, we report a potential new treatment that combines azole antifungals with bisphosphonates. Bisphosphonates are approved for the treatment of low bone density diseases, and in fungi they inhibit the biosynthesis of the cell membrane, which is also the target of azoles. Combinations were synergistic across the dermatophyte species and prevented the development of resistance. We extended the study to molds that cause invasive disease, finding synergy in some problematic species. We suggest bisphosphonates could be repurposed as synergents for tinea treatment, and that this combination could be fast-tracked for use in clinical therapy.


Subject(s)
Antifungal Agents , Arthrodermataceae , Diphosphonates , Drug Synergism , Microbial Sensitivity Tests , Antifungal Agents/pharmacology , Arthrodermataceae/drug effects , Humans , Diphosphonates/pharmacology , Azoles/pharmacology , Biofilms/drug effects , Drug Resistance, Fungal , Fungi/drug effects
8.
Clin Lab ; 70(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38868878

ABSTRACT

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.


Subject(s)
Arthrodermataceae , Onychomycosis , Humans , Onychomycosis/microbiology , Onychomycosis/diagnosis , Female , Arthrodermataceae/isolation & purification , Arthrodermataceae/genetics , Male , Turkey/epidemiology , Adult , Middle Aged , Aged , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Young Adult , Adolescent , Trichophyton/isolation & purification , Trichophyton/genetics , Molecular Diagnostic Techniques/methods , Coinfection/microbiology , Coinfection/diagnosis , Coinfection/epidemiology
10.
Mycopathologia ; 189(4): 59, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890181

ABSTRACT

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.


Subject(s)
Arthrodermataceae , Biofilms , Gene Expression Profiling , Photochemotherapy , Biofilms/drug effects , Arthrodermataceae/drug effects , Arthrodermataceae/genetics , Microsporum/drug effects , Microsporum/genetics , Humans , Antifungal Agents/pharmacology , Onychomycosis/microbiology , Onychomycosis/drug therapy , Transcriptome
11.
Expert Rev Anti Infect Ther ; 22(6): 399-412, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38841996

ABSTRACT

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.


Subject(s)
Antifungal Agents , Azoles , Drug Resistance, Fungal , Onychomycosis , Humans , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Antifungal Agents/pharmacology , Onychomycosis/drug therapy , Onychomycosis/microbiology , Azoles/administration & dosage , Azoles/pharmacology , Dermatomycoses/drug therapy , Dermatomycoses/microbiology , Off-Label Use , Drug Interactions , Arthrodermataceae/drug effects
12.
Biomed Khim ; 70(3): 180-186, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38940208

ABSTRACT

A novel series of 5'-benzylidene-3'-phenylspiro[indoline-3,2'-thiazolidine]-2,4'(1H)-diones 6a-d and spiro[indoline-3,2'-thiazolo[5,4-e]pyrimido[1,2-a]pyrimidin]-2(1H)-one 9a-d derivatives have been synthesized. All the newly synthesized compounds were evaluated for antifungal and anti-candidiasis activity by using Disc Diffusion and Modified Microdilution methods. The antimicrobial experiments have shown that the synthesized compounds demonstrated broad-spectrum antifungal activity in vitro. Among them, compounds 9a-9d had stronger antifungal activity against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans; compounds 6a-d also showed significant antifungal activity against selected fungal strains as compared to ketoconazole, the reference antifungal drug. The evaluation of antifungal activity against drug-resistant fungal variants showed that the designed compounds had significant antifungal activity against the tested variants. The combination of compounds (6a-d) and (9a-d) exhibited that the synthesized compounds had synergistic effects or additive effects. These results demonstrated that the synthesized compounds were putative chitin synthase inhibitors exhibiting broad spectrum antifungal activities. The present results indicate that novel spiro pyrimidine derivatives can be used as an active pharmaceutical ingredient for novel drug candidate for treatment of dermatophytosis and other fungal agents.


Subject(s)
Antifungal Agents , Arthrodermataceae , Candida albicans , Pyrimidines , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/chemical synthesis , Candida albicans/drug effects , Pyrimidines/pharmacology , Pyrimidines/chemistry , Pyrimidines/chemical synthesis , Arthrodermataceae/drug effects , Microbial Sensitivity Tests , Spiro Compounds/pharmacology , Spiro Compounds/chemistry , Spiro Compounds/chemical synthesis , Trichophyton/drug effects , Humans
13.
Biomater Adv ; 162: 213930, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38909600

ABSTRACT

An estimated 1.7 million fatalities and 150 million cases worldwide are attributed to fungal infections annually, that are in rise due to immunocompromised patient population. The challenges posed by traditional treatments can be addressed with the help of nanotechnology advancements. In this study, Co, Cu, and Ag-were doped into silica nanoparticles. Then the synthesized monometallic silica nanohybrids were combined to formulate heterometallic silica nanohybrids, characterized structurally and morphologically, compared, and evaluated for antifungal activity based on their individual and synergistic activity. The antifungal assays were conducted by using ATCC cultures of Candida albicans and QC samples of Trichophyton rubrum, Microsporum gypseum, and Aspergillus niger. The MIC (ranging from 49.00 to 1560.00 µg/mL), MFC (ranging from 197.00 to 3125.00 µg/mL), IC50 values (ranging from 31.10 to 400.80 µg/mL), and FICI of nanohybrids were determined and compared. Moreover, well diffusion assay was performed. ABTS assay and DPPH assay were conducted to investigate the radical scavenging activity (RSA) of nanohybrids. SEM analysis clearly evidenced the structural deformations of each fungal cells and spores due to the treatment with trimetallic nanohybrid. According to the results, the trimetallic silica nanohybrids exhibited the most powerful synergistic RSA and the most effective antifungal activity, compared to the bimetallic silica nanohybrids.


Subject(s)
Antifungal Agents , Candida albicans , Microbial Sensitivity Tests , Silicon Dioxide , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/chemical synthesis , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , Candida albicans/drug effects , Aspergillus niger/drug effects , Nanoparticles/chemistry , Microsporum/drug effects , Drug Synergism , Copper/chemistry , Copper/pharmacology , Silver/pharmacology , Silver/chemistry , Arthrodermataceae
14.
J Basic Microbiol ; 64(7): e2400112, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38770635

ABSTRACT

Dermatophytosis is a cutaneous infection that is able to degrade the keratinized tissues of the animal/human body, like skin, nails, and hair, causing chronic or subacute infection with the contact of some specific fungal strains. Trichophyton mentagrophytes are the most potential fungal pathogen causing dermatophytoses. The present study focuses on computationally based in silico antifungal activity of selected phytocompounds of Leucas aspera (Willd.) Link. against dermatophytic fungus, T. mentagrophytes. Validation and screening of derived phytocompounds is performed using Lipinski rule of five and toxicity test through Protox-II. Five target genes involved in dermatophytosis, induced by T. mentagrophytes are retrieved from the UniProt Database, and the corresponding proteins such as glucan 1,3-beta-glucosidase ARB_02797, Probable class II chitinase ARB_00204, squalene monooxygenase, actin, and ubiquitin are selected for in silico study. Three-dimensional structures of the target protein were computationally determined and validated through modeling tools and techniques due to the lack of validated protein structures in the database. Then, these proteins are used for in silico molecular docking through the AutoDock Vina tool to find out the promising phytocompounds. This study could be utilized in designing more effective drugs against T. mentagrophytes. Based on this work, a plant-based natural alternative can be added to the treatment of dermatophytosis rather than synthetic supplements.


Subject(s)
Antifungal Agents , Molecular Docking Simulation , Phytochemicals , Phytochemicals/pharmacology , Phytochemicals/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Fungal Proteins/antagonists & inhibitors , Fungal Proteins/metabolism , Fungal Proteins/chemistry , Arthrodermataceae/drug effects , Tinea/microbiology , Tinea/drug therapy , Squalene Monooxygenase/antagonists & inhibitors , Squalene Monooxygenase/metabolism , Squalene Monooxygenase/chemistry , Humans , Computer Simulation , Chitinases/metabolism , Chitinases/antagonists & inhibitors , Plant Extracts/pharmacology , Plant Extracts/chemistry , Computational Biology , Actins/metabolism
15.
Mycopathologia ; 189(3): 37, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704808

ABSTRACT

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.


Subject(s)
Alternative Splicing , Arthrodermataceae , Gene Expression Regulation, Fungal , Mitogen-Activated Protein Kinases , Tinea , Transcription Factors , Humans , Arthrodermataceae/genetics , Arthrodermataceae/metabolism , Glucose/metabolism , Keratinocytes/microbiology , Keratins/metabolism , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , Real-Time Polymerase Chain Reaction , Transcription Factors/genetics , Transcription Factors/metabolism , Tinea/metabolism , Tinea/microbiology
16.
Pak J Pharm Sci ; 37(2): 257-263, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38767092

ABSTRACT

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.


Subject(s)
Antifungal Agents , Arthrodermataceae , Cedrus , Microbial Sensitivity Tests , Microsporum , Microsporum/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/isolation & purification , Arthrodermataceae/drug effects , Cedrus/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/chemistry , Gas Chromatography-Mass Spectrometry , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Phytochemicals/analysis , Phytochemicals/chemistry , Morocco
17.
Acta Trop ; 255: 107237, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723739

ABSTRACT

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.


Subject(s)
Antifungal Agents , Cat Diseases , Microsporum , Tinea , Cats/microbiology , Animals , Cat Diseases/microbiology , Cat Diseases/drug therapy , India/epidemiology , Tinea/veterinary , Tinea/microbiology , Tinea/drug therapy , Tinea/epidemiology , Antifungal Agents/therapeutic use , Microsporum/isolation & purification , Microsporum/genetics , Male , Female , Arthrodermataceae/isolation & purification , Arthrodermataceae/genetics , Arthrodermataceae/classification , Arthrodermataceae/drug effects , Itraconazole/therapeutic use , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , DNA, Fungal/genetics , DNA, Ribosomal Spacer/genetics
18.
J Ethnopharmacol ; 331: 118344, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38754641

ABSTRACT

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.


Subject(s)
Antifungal Agents , Artemisia , Arthrodermataceae , Oils, Volatile , Oxidative Phosphorylation , Oxidative Stress , Artemisia/chemistry , Antifungal Agents/pharmacology , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Arthrodermataceae/drug effects , Oxidative Stress/drug effects , Oxidative Phosphorylation/drug effects , Microbial Sensitivity Tests , Gas Chromatography-Mass Spectrometry
19.
Rev. chil. infectol ; 41(2): 218-224, abr. 2024. ilus, tab
Article in Spanish | LILACS | ID: biblio-1559677

ABSTRACT

Los dermatofitos son un grupo de hongos responsables de las dermatofitosis o tiñas, pudiendo afectar piel, uñas y pelo. En la actualidad están constituidos por los géneros Epidermophyton, Trichophyton, Microsporum, Arthroderma, Paraphyton, Lophophyton y Nannizzia. El examen microscópico directo y el cultivo en agar siguen siendo el estándar de oro para la identificación, sin embargo, en ocasiones se requiere de la biología molecular para poder corroborar una determinada especie. Dependiendo de la localización, del número de lesiones y de la extensión, el tratamiento de las dermatofitosis puede ser tópico o sistémico. Trichophyton indotineae y T tonsurans pueden expresar resistencia a la terbinafina y azoles, respectivamente.


Dermatophytes are a group of fungi responsible for dermatophytosis or ringworm, which can affect the skin, nails and hair. Currently, they are assembled by the genera Epidermophyton, Trichophyton, Microsporum, Arthroderma, Paraphyton, Lophophyton and Nannizzia. Direct microscopic examination and culture on agar remain the gold standard for identification, however, molecular biology is sometimes required to confirm a certain species. Depending on the location, the number of lesions and the extension, the treatment of dermatophytosis can be topical or systemic. Trichophyton indotineae and T tonsurans can express resistance to terbinafine and azoles, respectively.


Subject(s)
Humans , Tinea/diagnosis , Tinea/drug therapy , Arthrodermataceae/classification
20.
Med Mycol ; 62(7)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38653717

ABSTRACT

Tinea capitis (TC) is still a frequent dermatophytosis in France, both autochthonous and imported. A nationwide retrospective survey was performed and a total of 4395 TC cases were recorded within 36 French mycology laboratories during a 6-year period. TC is a disease that occurs in childhood with 85% of the cases occurring before 10 years old and 94% before the age of 15. Anthropophilic origin was predominant with 779 cases of Trichophyton tonsurans (32.6%), 738 cases of Trichophyton soudanense/T. violaceum (31%), and 445 cases of Microsporum audouinii (19.2%). Of note, T. tonsurans represents more than 80% of the cases in the French West Indies (Martinique and Guadeloupe). By contrast, zoophilic species were less prevalent with mainly M. canis (10.3%) confirming the shift from zoophilic to anthropophilic species observed in many centers during the last decades. During this survey, diagnosis methods were also collected. Most labs had a classical process for the diagnosis: microscopic direct examination associated to cultures on Sabouraud and Sabouraud-cycloheximide media (incubated between 25 ± 5°C for at least 3 weeks) in all laboratories. Identification of the causal dermatophyte was performed by microscopic and macroscopic examination of the cultures in 100% of the labs, with various specific culture media available when fructification was insufficient (mainly malt or potato-dextrose agar, or Borelli medium). New techniques were also implemented with the introduction of MALDI-TOF mass spectrometry identification in more than two third of the labs, and molecular identification available if necessary in half of the labs.


A total of 4395 tinea capitis cases were recorded within 36 French mycology laboratories during a 6-year period. An anthropophilic origin was predominant with 33%, 31%, and 18.8% of cases due to Trichophyton tonsurans, T. soudanense/T. violaceum, and Microsporum audouinii, respectively.


Subject(s)
Microsporum , Tinea Capitis , Humans , Tinea Capitis/epidemiology , Tinea Capitis/microbiology , Tinea Capitis/drug therapy , Retrospective Studies , France/epidemiology , Child , Microsporum/isolation & purification , Adolescent , Child, Preschool , Male , Female , Arthrodermataceae/isolation & purification , Arthrodermataceae/classification , Trichophyton/isolation & purification , Prevalence , Surveys and Questionnaires , Infant , Adult
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