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Under steady-state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiotaspecific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi preexposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.

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 Phe 397 Leu substitution. A non-previously described point mutation, Phe 311 Leu was identified in T. indotineae and mutations Lys 276 Asn, Phe 397 Leu and Leu 419 Phe were diagnosed in T. mentagrophytes XVII. The results of mutation analysis showed that Phe 397 Leu 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.

Dermatophytes represent the largest and most common group of fungal infections, impacting 25% of the global population. Among them, Trichophyton rubrum has emerged as the predominant species, responsible for a range of conditions such as tinea corporis, tinea pedis, onychomycosis, tinea cruris, and tinea manuum. Although dermatophyte incidence varies geographically, there is a noticeable rise in cases caused by T. indotineae , a strain that exhibits resistance to terbinafine. In the past decade zoophilic dermatophyte T. mentagophytes genotype VII (now known as T. interdigitale ) gains a growing importance, due to its increasing frequency, the severity of the clinical manifestation and mode of transmission. Tinea infections present with various clinical symptoms and can affect individuals of all ages, from tinea pedis in adults to tinea capitis in children. Among adults globally, tinea unguium (onychomycosis) is the most common form of dermatophytosis, affecting 5.5% of the general population. Tinea unguium is more frequently seen in developed countries, while tinea capitis is more common in developing nations. The COVID-19 pandemic has led to an increase in cases of tinea faciei, likely due to prolonged mask-wearing. Terbinafine remains the preferred treatment for dermatophyte infections worldwide due to its potent fungicidal properties, minimal risk of drug interactions, and fewer side effects compared to other oral antifungals. Itraconazole and terbinafine appear to be equally effective and safe for treating tinea cruris and tinea corporis. However, the rising resistance of dermatophytes to these antifungal drugs, along with frequent recurrences of dermatophytosis in certain regions, is becoming a significant public health concern.

The objective of this study was to find one or more fungal strains that could be utilized to biosynthesize antifungal silver nanoparticles (AgNPs). Using morphological and molecular methods, Arthroderma fulvum was identified as the most effective fungal strain for synthesizing AgNPs. The UV-visible range showed a single peak at 420 nm, which corresponded to the surface plasmon absorbance of AgNPs. X-ray diffraction and transmission electron microscopy demonstrated that the biosynthesized AgNPs were crystalline in nature with an average diameter of 15.5±2.5 nm. Numerous factors could potentially affect the process of biosynthesis, and the main factors are discussed here. Optimization results showed that substrate concentration of 1.5 mM, alkaline pH, reaction temperature of 55°C, and reaction time of 10 hours were the optimum conditions for AgNP biosynthesis. Biosynthesized AgNPs showed considerable activity against the tested fungal strains, including Candida spp., Aspergillus spp., and Fusarium spp., especially Candida spp.

Background & objectives Dermatophytes are accountable for the majority of fungal skin infections globally, affecting 20-25 per cent of the world population. Though not fatal, these infections have significant psychosocial impacts and reduce the quality of life. Prevalence of the infection varies geographically, influenced by factors like social practices, migration and climate. Understanding the pathogenicity of dermatophytosis including virulence factors and drug resistance, is necessary to identify factors that predispose recalcitrance. Methods A prospective hospital-based study was carried out in the dermatology departments of two tertiary care hospitals in Mangaluru, India from November 2018 to March 2021. We included 93 individuals of recalcitrant tinea infections, and excluded those with diabetes or those under immunosuppressive therapy. Skin scrapings from lesions were cultured, and DNA extracted for ITS sequencing. All samples were processed for antifungal susceptibility testing, and mutation analysis in squalene epoxidase gene for representative isolates and virulence factor assays. Results Of 93 clinically diagnosed individuals with dermatophytosis, dermatophytes were recovered in 70.96 per cent samples, with Trichophyton mentagrophytes complex being the most common agent. Antifungal susceptibility testing showed high MICs for fluconazole, terbinafine and itraconazole in several isolates, indicating in-vitro resistance. Mutation analysis for six isolates revealed missense mutations in the squalene epoxidase gene. Virulence activity analysis showed high enzyme production levels among isolates, contributing to their pathogenicity. Interpretation & conclusions These findings underscore the complexity of dermatophytosis and emphasize the need for persistent tracking of antifungal resistance patterns and virulence factors. Such insights are vital for developing effective treatment strategies and improving patient outcomes due to rising antifungal resistance.

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics 1 . Here we show that particular lineages of methicillin-resistant Staphylococcus aureus —a notorious human pathogen—appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development. Methicillin-resistant strains of Staphylococcus aureus appeared in European hedgehogs in the pre-antibiotic era as a co-evolutionary adaptation to antibiotic-producing dermatophytes and have spread within the local hedgehog populations and between hedgehogs and secondary hosts.

Background Novel treatments against for tinea capitis are needed, and the natural aminosterol squalamine is a potential topical antidermatophyte drug candidate. Objectives This phase II randomized double-blind placebo-controlled clinical trial aimed at testing the efficacy and safety of a three-week squalamine ointment regimen for the treatment of tinea capitis . Patients Males aged 6–15 years presenting with tinea capitis were treated with either topical squalamine ointment or placebo for 3 weeks. The primary endpoint was complete clinical cure. The secondary endpoints were the occurrence of local and/or systemic adverse events, mycological cure, and partial clinical response. Prospective follow-up of clinical adverse events was performed daily. Results Five patients were treated with 1 % squalamine ointment and 15 with placebo. No complete cure was observed. No clinical or biological adverse event was recorded. A significantly ( p  = 0.03) better hair-growth score, indicating a partial clinical improvement of the tinea capitis lesion, was observed in the patients treated with squalamine compared to those treated with placebo. Conclusion This three-week squalamine ointment regimen was well tolerated and showed an encouraging partial clinical activity for the treatment of tinea capitis . Further studies are needed to evaluate the efficacy of topical squalamine alone against tinea corporis or in combination with a systemic antidermatophyte drug against tinea capitis .

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.

With regard to increasing number of antifungal-resistant dermatophytes, antifungal susceptibility testing of dermatophytes serves as a useful tool in managing clinical dermatophytosis. This study aimed to determine antifungal susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolates. Based on our results, dermatophytosis was confirmed in 97 cases by direct microscopic examination, culture, and sequencing of ITS region. Antifungal susceptibility of 97 dermatophyte isolates distributed in four species including Trichophyton interdigitale (26 isolates), T. rubrum (19 isolates), T. tonsurans (29 isolates), and Epidermophyton floccosum (21 isolates) was assessed to nine antifungal agents using CLSI M38-A2 guidelines. Minimum inhibitory concentration range (MIC range) for luliconazole and terbinafine was 0.001–0.008 μg/ml and 0.003–> 32 μg/ml, compared to 0.03–64 μg/ml for griseofulvin, 0.01–16 μg/ml for itraconazole and voriconazole, 0.03–8 μg/ml for ketoconazole, 0.03–32 μg/ml for econazole, 0.03–1 μg/ml for lanoconazole, and 0.01–4 μg/ml for butenafine. Trichophyton tonsurans was the most susceptible (MIC = 0.006 μg/ml) and E. floccosum was the most resistant (MIC = 0.02 μg/ml) species to terbinafine. Terbinafine resistance was reported for two species, i.e., T. rubrum and T. tonsurans at the total rate of 2% which was due to Leu393Phe substitution in both species. Taken together, our results assist clinicians and prompt the current knowledge about the necessity of antifungal susceptibility testing to select effective strategies for management of clinical cases of dermatophytosis.

Background: Cutaneous infections caused by dermatophytes and non-dermatophytes fungi have become significant public health and veterinary concern.Objective: The current study deals with the distribution, characterization, and antifungal susceptibility profile of these fungi. Materials and Methods: A total of 40 sample were screened by KOH mount; positive samples were cultured on SDA. Purified isolates were identified by macroscopic and microscopic characters. Molecular characterization by PCR and sanger sequencing of ITS region confirmed the fungi. Evolutionary trees were constructed using MEGA 11. Different treatment options were evaluated, including amphotericin B, nystatin, fluconazole, itraconazole, and essential oil of Nigella sativa. Initially molecular docking was performed against selected fungal targets (5eqb and 5v5z) using molecular-operating environment (MOE v.2018.01) and Maestro modeling interface 12.3. In vitro antimycotic activity was performed by agar disc diffusion, followed by microbroth dilution method. Results: KOH mount revealed that 65% (13/20) samples positive for fungal components. Culture positivity for samples was 23.07% for dermatophytes and 76.92% for non-dermatophytes. Dermatophytes were detected in skin samples. However, non-dermatophytes were isolated from all types of samples. Sequence analysis confirmed the distribution of Arthroderma multifidum, Aspergillus sydowii, and Aspergillus sublatus. In-silico analysis revealed itraconazole as the most effective antimycotic agent with -7.93 kcal/mol (5eqb) and -10.89 (5v5z) kcal/mol. In vitro analysis strengthens docking analysis, itraconazole was the most effective agent with the highest mean ZOI against A. multifidum (72.00±3.46 mm), A. sydowii (62.00±3.00 mm), and A. sublatus (64.00±1.73 mm). Moreover, essential oil of N. sativa was the most effective antifungal against A. sydowii (ZOI; 31.00±3.46 mm, MIC; 3.125±0.00 mg/mL). Conclusion: The current study is the first report of A. sydowii and A. sublatus in onychomycosis and hair infections in Pakistan. This study provides awareness about the existence of new fungal pathogens and highlights the availability of effective treatment options for emerging fungal infections.