Clinico-mycological study of onychomycosis and in vitro antifungal susceptibility of Trichophyton rubrum.

Onychomycosis, a fungal nail infection, is primarily caused by dermatophytes, yeasts, and non-dermatophyte moulds (NDMs). The incidence of this disease and the predominance of specific pathogens vary across different regions and evolve. This study aimed to elucidate the epidemiology of onychomycosis and the pattern of causative pathogens in Beijing, and to ascertain the in vitro antifungal susceptibility profiles of Trichophyton rubrum against itraconazole (ITR), terbinafine (TER), and fluconazole (FLU). Involving 245 patients of onychomycosis with positive fungal culture results, the study implemented internal transcribed spacer (ITS) sequencing of ribosomal DNA (rDNA) on all collected samples. The mean age of the participants was 37.93 ± 13.73 years, with a male-to-female ratio of 1.53:1. The prevalence of toenail infections was significantly higher than that of fingernails. Distal and lateral subungual onychomycosis (DLSO) were the most frequent clinical classifications. PCR results indicated that dermatophytes were the most prevalent pathogens, followed by yeasts and NDMs, among which T. rubrum was the most dominant dermatophyte. TER demonstrated high sensitivity to T. rubrum. However, in clinical settings, some patients with onychomycosis exhibit a poor response to TER treatment. The relationship between in vitro antifungal sensitivity and clinical effectiveness is complex, and understanding the link between in vitro MIC values and clinical efficacy requires further investigation.

In vitro antifungal activity of polymeric nanoparticles loaded with Euphorbia tirucalli extract.

The therapeutic potential of medicinal plants is known as an alternative in treatment of human affections; in effect, the conventional application of these medicinal sources has several limitations like low bioavailability, solubility and stability, which affect its pharmacological efficacy. In recent decades, extraordinary advances have been made in new drug delivery systems using nanocarriers. This work consisted in determining the in vitro antifungal activity of the methanolic extract of Euphorbia tirucalli formulated in polymeric nanoparticles. The antifungal activity was determined by the microdilution method in 96-well microplates, applying nanoparticles loaded with plant extract (NP-Ext) obtained by nanoprecipitation on clinical isolates of Trichophyton rubrum and T. interdigitalis. Regarding the nanoparticles, the lots used did not present significant differences in their physicochemical characteristics, with a size of 91.885 ± 1.621nm, polydispersity index of 0.152 ± 0.025 and Z-potential of -6.047 ± 0.987. The quantification of the extract in the polymeric matrix was determined by infrared spectroscopy (FTIR), where an efficiency and encapsulation percentage of 22.15 ± 0.82 and 2.95 ± 0.11, respectively, were obtained. The in vitro antifungal activity of the crude and formulated extract was obtained calculating the Minimum Inhibitory Concentration (MIC) of each one; a MIC of 125 µg/mL was obtained against T. rubrum and T. interdigitalis with the crude extract, while a MIC value of 55.55 and 0.1 µg/mL was obtained with NP-Ext, respectively, against these same. Conclusions: biological activity is closely linked to the phytochemical profile of the extract; while the improvement of said potential with the NP-Ext with the dosage form was directly related to the physicochemical characteristics of the nanocarrier.

Formulation and Antimycotic Evaluation of Colloidal Itraconazole-Loaded Metered Dose Sprays for Treating Superficial Mycoses.

Commercial topical formulations containing itraconazole (poorly water soluble), for mycotic infections, have poor penetration to infection sites beneath the nails and skin thereby necessitating oral administration. To improve penetration, colloidal solutions of itraconazole (G1-G4) containing Poloxamer 188, tween 80, ethanol, and propylene glycol were prepared and incorporated into HFA-134-containing sprays. Formulations were characterized using particle size, drug content, and Fourier-transform infrared spectroscopy (FTIR). In vitro permeation studies were performed using Franz diffusion cells for 8 h. Antimycotic activity on Candida albicans and Trichophyton rubrum was performed using broth micro-dilution and flow cytometry, while cytotoxicity was tested on HaCaT cell lines. Particle size ranged from 39.35-116.80 nm. FTIR and drug content revealed that G1 was the most stable formulation (optimized formulation). In vitro release over 2 h was 45% for G1 and 34% for the cream. There was a twofold increase in skin permeation, fivefold intradermal retention, and a sevenfold increase in nail penetration of G1 over the cream. Minimum fungicidal concentrations (MFC) against C. albicans were 0.156 and 0.313 µg/mL for G1 and cream, respectively. The formulations showed optimum killing kinetics after 48 h. MFC values against T. rubrum were 0.312 and 0.625 µg/mL for the G1 and cream, respectively. Transmission electron microscopy revealed organelle destruction and cell leakage for G1 in both organisms and penetration of keratin layers to destroy T. rubrum. Cytotoxicity evaluation of G1 showed relative safety for skin cells. The G1 formulation showed superior skin permeation, nail penetration, and fungicidal activity compared with the cream formulation.

Diagnostic ability of Peptidase S8 gene in the Arthrodermataceae causing dermatophytoses: A metadata analysis.

An unambiguous identification of dermatophytes causing dermatophytoses is necessary for accurate clinical diagnosis and epidemiological implications. In the current taxonomy of the Arthrodermataceae, the etiological agents of dermatophytoses consist of seven genera and members of the genera Trichophyton are the most prevalent etiological agents at present. The genera Trichophyton consists of 16 species that are grouped as clades, but the species borderlines are not clearly delimited. The aim of the present study was to determine the discriminative power of subtilisin gene variants (SUB1-SUB12) in family Arthrodermataceae, particularly in Trichophyton. Partial and complete reads from 288 subtilisin gene sequences of 12 species were retrieved and a stringent filtering following two different approaches for analysis (probability of correct identification (PCI) and gene gap analysis) conducted to determine the uniqueness of the subtilisin gene subtypes. SUB1 with mean PCI value of 60% was the most suitable subtilisin subtype for specific detection of T.rubrum complex, however this subtype is not reported in members of T. mentagrophytes complex which is one of the most prevalent etiological agent at present. Hence, SUB7 with 40% PCI value was selected for testing its discriminative power in Trichophyton species. SUB7 specific PCR based detection of dermatophytes was tested for sensitivity and specificity. Sequences of SUB7 from 42 isolates and comparison with the ITS region showed that differences within the subtilisin gene can further be used to differentiate members of the T. mentagrophytes complex. Further, subtilisin cannot be used for the differentiation of T. benhamiae complex since all SUB subtypes show low PCI scores. Studies on the efficiency and limitations of the subtilisin gene as a diagnostic tool are currently limited. Our study provides information that will guide researchers in considering this gene for identifying dermatophytes causing dermatophytoses in human and animals.

Potential emergence of terbinafine resistance by squalene epoxidase gene mutations: An 18-month cohort study of onychomycosis patients in the United States.

BACKGROUND: There is a concerning rise in antifungal-resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. OBJECTIVES: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. CONCLUSION: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.

A survey of 701 cases of tinea faciei in Hangzhou, southeastern China, from 2018 to 2023.

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.

Comparative Transcriptome Analysis of T. rubrum, T. mentagrophytes, and M. gypseum Dermatophyte Biofilms in Response to Photodynamic Therapy.

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.

Potential antifungal applications of heterometallic silica nanohybrids: A synergistic activity.

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.

Novel spiro[indoline-3,2'thiazolo[5,4-e]pyrimido[1,2-a] pyrimidine] derivatives as possible anti-dermatophytic and anti-candidiasis agent.

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.

Bisphosphonates synergistically enhance the antifungal activity of azoles in dermatophytes and other pathogenic molds.

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.

Molecular Detection of Dermatophytes and Nondermatophytes in Onychomycosis in Antalya, Turkey.

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.

High Prevalence of Terbinafine Resistance Among Trichophyton mentagrophytes/T. interdigitale Species Complex, a Cross-Sectional Study from 2021 to 2022 in Northern Parts of Iran.

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.

Epidemiology of Tinea Capitis Among School-Children in Dschang, Western Cameroon.

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.

Safety and efficacy of new generation azole antifungals in the management of recalcitrant superficial fungal infections and onychomycosis.

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.

Epidemiological trends, antifungal drug susceptibility and SQLE point mutations in etiologic species of human dermatophytosis in Al-Diwaneyah, Iraq.

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.

Tinea faciei clinical characteristics, causative agents, treatments and outcomes; a retrospective study in Thailand.

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.

The StuA Transcription Factor and Alternative Splicing Mechanisms Drive the Levels of MAPK Hog1 Transcripts in the Dermatophyte Trichophyton rubrum.

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.

Phytochemical inhibitors from Leucas aspera against the target proteins induced by Trichophyton mentagrophytes using computational techniques.

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.