Malassezia Yeasts Research Articles

Malassezia gallinae sp. nov., a new basidiomycetous yeast species isolated from skins of chickens.

Species of Malassezia are lipid-dependent yeasts and integral components of the skin microbiome. Most of the currently known species are isolated from mammals. However, the presence and distribution of Malassezia yeasts on the skin of avian species have not been fully understood or elucidated. During a survey on the occurrence of Malassezia species in chickens, 23 Malassezia strains isolated from the healthy skins of chickens may represent two candidate new species of this genus based on the sequence analysis of the internal transcribed spacer (ITS) (including 5.8S rRNA) and the D1/D2 domains of 26S rRNA. The combined ITS and D1/D2 phylogenetic analysis showed that those two candidate new species were closely related to Malassezia slooffiae, and differed from the type of M. slooffiae by 51-62 nucleotides in the ITS region and four nucleotides in the D1/D2 domains, respectively. Based on the phylogenetic analysis and the phenotypic comparison, we propose a new species, named Malassezia gallinae sp. nov., to include the 21 isolated strains.

Azelaic Acid: Mechanisms of Action and Clinical Applications.

AZA is a non-phenolic, saturated dicarboxylic acid with nine carbon atoms, naturally produced by the yeast Malassezia. It has diverse physiological activities, including antibacterial, anti-keratinizing, antimelanogenic, antioxidant and anti-inflammatory effects. AZA is widely used in dermatology and is FDA-approved for treating papulopustular rosacea. It also shows significant efficacy in acne vulgaris and melasma. This review summarizes the mechanisms of action and clinical applications of AZA, aiming to provide theoretical support for its clinical and cosmetic use and to facilitate further research.

Successful Treatment of Seborrheic Dermatitis with Topical Roflumilast: A Case Series

Background: Seborrheic dermatitis (SD) is a common skin disease that presents with pink scaly patches in areas with higher sebaceous gland density, such as the scalp, glabella, retroauricular folds, nasolabial folds, chest, and groin. Case Reports: This is a case series of two patients with longstanding SD that did not respond adequately to topical corticosteroids or azoles, and were successfully treated monotherapy with roflumilast cream 0.3%. Both patients responded within two months and continue to respond to treatment with topical roflumilast monotherapy. Discussion: SD is commonly considered to be caused by Malassezia yeast proliferation and activity, however recent research has revealed that the inflammatory skin disease results from immune dysregulation and skin barrier disruption with Malassezia contributing as an exacerbating factor secondary to the primary pathogenesis. Thus treatment with topical roflumilast, a highly potent phosphodiesterase-4 inhibitor, has been studied and demonstrated to be effective in treating the signs and symptoms of SD. Topical roflumilast 0.3% is formulated as a cream and a foam, with the foam approved for the treatment of SD. These cases demonstrate a successful treatment of patients with longstanding SD with roflumilast cream 0.3%. Conclusion: These cases demonstrate that SD, treated with either roflumilast cream 0.3% or roflumilast foam 0.3% may provide improvement in signs and symptoms of SD.

Flourishing in Darkness: Protist Communities of Water Sites in Shulgan-Tash Cave (Southern Urals, Russia)

Karst caves, formed by the erosion of soluble carbonate rocks, provide unique ecosystems characterized by stable temperatures and high humidity. These conditions support diverse microbial communities, including wall microbial fouling, aquatic biofilms, and planktonic communities. This study discloses the taxonomic diversity of protists in aquatic biotopes of Shulgan-Tash Cave, a culturally significant site and popular tourist destination, by 18S rRNA gene metabarcoding. Our findings reveal the rich protist communities in the cave’s aquatic biotopes, with the highest diversity observed in Blue Lake at the cave entrance. In contrast, Distant Lake in the depth of the cave was inhabited by specific communities of plankton, mats, and pool fingers, which exhibited lower richness and evenness, and were adapted to extreme conditions (cold, darkness, and limited nutrients). High-rank taxa including Opisthokonta, Stramenopiles, and Rhizaria dominated all biotopes, aligning with observations from other subterranean environments. Specific communities of biotopes inside the cave featured distinct dominant taxa: amoeboid stramenopile (Synchromophyceae) and flagellates (Choanoflagellatea and Sandona) in mats; flagellates (Choanoflagellatea, Bicoecaceae, Ancyromonadida) and amoeboid protists (Filasterea) in pool fingers; flagellates (Ochromonadales, Glissomonadida, Synchromophyceae), fungi-like protists (Peronosporomycetes), and fungi (Ustilaginomycotina) in plankton. The specificity of the communities was supported by LEfSe analysis, which revealed enriched or differentially abundant protist taxa in each type of biotope. The predominance of Choanoflagellatea in the communities of cave mats and pool fingers, as well as the predominance of Synchromophyceae in the cave mats, appears to be a unique feature of Shulgan-Tash Cave. The cold-tolerant yeast Malassezia recorded in other caves was present in both plankton and biofilm communities, suggesting its resilience to low temperatures. However, no potentially harmful fungi were detected, positioning this research as a baseline for future monitoring. Our results emphasize the need for ongoing surveillance and conservation efforts to protect the fragile ecosystems of Shulgan-Tash Cave from human-induced disturbances and microbial invasions.

Combinatory Use of hLF(1-11), a Synthetic Peptide Derived from Human Lactoferrin, and Fluconazole/Amphotericin B against Malassezia furfur Reveals a Synergistic/Additive Antifungal Effect.

The increasing resistance of Malassezia yeasts against commonly used antifungal drugs dictates the need for novel antifungal compounds. Human lactoferrin-based peptides show a broad spectrum of antimicrobial activities. Various assays were performed to find the optimal growth conditions of the yeasts and to assess cell viability, using media with low lipid content to avoid peptide binding to medium components. In the current study, we tested the antimicrobial susceptibility of 30 strains of M. furfur that cover the known IGS1 genotypic variation. hLF(1-11) inhibited the growth of all species tested, resulting in minimum inhibitory concentrations (MIC) values ranging from 12.5 to 100 μg/mL. In the combinatory tests, the majority of fractional inhibitory concentration indexes (FIC) for the tested strains of M. furfur were up to 1.0, showing that there is a synergistic or additive effect on the efficacy of the antifungal drugs when used in combination with hLF(1-11). Results showed that hLF(1-11) could be combined with fluconazole or amphotericin for the antimicrobial treatment of resistant strains, enhancing the potency of these antifungal drugs, resulting in an improved outcome for the patient.

A New Generation of Postbiotics for Skin and Scalp: In Situ Production of Lipid Metabolites by Malassezia.

Effects of pre- and probiotics on intestinal health are well researched and microbiome-targeting solutions are commercially available. Even though a trend to appreciate the presence of certain microbes on the skin is seeing an increase in momentum, our understanding is limited as to whether the utilization of skin-resident microbes for beneficial effects holds the same potential as the targeted manipulation of the gut microflora. Here, we present a selection of molecular mechanisms of cross-communication between human skin and the skin microbial community and the impact of these interactions on the host's cutaneous health with implications for the development of skin cosmetic and therapeutic solutions. Malassezia yeasts, as the main fungal representatives of the skin microfloral community, interact with the human host skin via lipid mediators, of which several are characterized by exhibiting potent anti-inflammatory activities. This review therefore puts a spotlight on Malassezia and provides a comprehensive overview of the current state of knowledge about these fungal-derived lipid mediators and their capability to reduce aesthetical and sensory burdens, such as redness and itching, commonly associated with inflammatory skin conditions. Finally, several examples of current skin microbiome-based interventions for cosmetic solutions are discussed, and models are presented for the use of skin-resident microbes as endogenous bio-manufacturing platforms for the in situ supplementation of the skin with beneficial metabolites.

Next generation mycological diagnosis: Artificial intelligence-based classifier of the presence of Malassezia yeasts in tape strip samples.

Malassezia yeasts are almost universally present on human skin worldwide. While they can cause diseases such as pityriasis versicolor, their implication in skin homeostasis and pathophysiology of other dermatoses is still unclear. Their analysis using native microscopy of skin tape strips is operator dependent and requires skill, training and significant amounts of hands-on time. To standardise and improve the speed and quality of diagnosis of Malassezia in skin tape strip samples, we sought to create an artificial intelligence-based algorithm for this image classification task. Three algorithms, each using different internal architectures, were trained and validated on a manually annotated dataset of 1113 images from 22 samples. The Vision Transformer-based algorithm performed the best with a validation accuracy of 94%, sensitivity of 94.0% and specificity of 93.5%. Visualisations providing insight into the reasoning of the algorithm were presented and discussed. Our image classifier achieved very good performance in the diagnosis of the presence of Malassezia yeasts in tape strip samples of human skin and can therefore improve the speed and quality of, and access to this diagnostic test. By expanding data sources and explainability, the algorithm could also provide teaching points for more novice operators in future.

Card9 and MyD88 differentially regulate Th17 immunity to the commensal yeast Malassezia in the murine skin.

The fungal community of the skin microbiome is dominated by a single genus, Malassezia. Besides its symbiotic lifestyle at the host interface, this commensal yeast has also been associated with diverse inflammatory skin diseases in humans and pet animals. Stable colonization is maintained by antifungal type 17 immunity. The mechanisms driving Th17 responses to Malassezia remain, however, unclear. Here, we show that the C-type lectin receptors Mincle, Dectin-1, and Dectin-2 recognize conserved patterns in the cell wall of Malassezia and induce dendritic cell activation in vitro, while only Dectin-2 is required for Th17 activation during experimental skin colonization in vivo. In contrast, Toll-like receptor recognition was redundant in this context. Instead, inflammatory IL-1 family cytokines signaling via MyD88 were also implicated in Th17 activation in a T cell-intrinsic manner. Taken together, we characterized the pathways contributing to protective immunity against the most abundant member of the skin mycobiome. This knowledge contributes to the understanding of barrier immunity and its regulation by commensals and is relevant considering how aberrant immune responses are associated with severe skin pathologies.

Cold atmospheric plasma therapy for Malassezia folliculitis: Laboratory investigations and a randomized clinical trial.

Current treatment options for Malassezia folliculitis (MF) are limited. Recent research has demonstrated the inhibitory effect of cold atmospheric plasma (CAP) on the growth of Malassezia pachydermatis in vitro, suggesting CAP as a potential therapeutic approach for managing MF. The objective of our study is to assess the in vitro antifungal susceptibility of Malassezia yeasts to CAP. Additionally, we aim to evaluate the efficacy and tolerability of CAP in treating patients with MF. We initially studied the antifungal effect of CAP on planktonic and biofilm forms of Malassezia yeasts, using well-established techniques such as zone of inhibition, transmission electron microscopy, colony count assay and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt assay. Subsequently, a randomized (1:1 ratio), active comparator-controlled, observer-blind study was conducted comparing daily CAP therapy versus itraconazole 200mg/day for 2weeks in 50 patients with MF. Efficacy outcomes were measured by success rate, negative microscopy rate and changes in Dermatology Life Quality Index (DLQI) and Global Aesthetic Improvement Scale (GAIS) scores. Safety was assessed by monitoring adverse events (AEs) and local tolerability. In laboratory investigations, CAP time-dependently inhibited the growth of Malassezia yeasts in both planktonic and biofilm forms. Forty-nine patients completed the clinical study. At week 2, success was achieved by 40.0% of subjects in the CAP group versus 58.3% in the itraconazole group (p=0.199). The negative direct microscopy rates of follicular samples were 56.0% in the CAP group versus 66.7% in the itraconazole group (p=0.444). No significant differences were found in the proportion of subjects achieving DLQI scores of 0/1 (p=0.456) or in the GAIS responder rates (p=0.588) between the two groups. Three patients in the CAP group and one patient in the itraconazole group reported mild AEs. CAP demonstrated significant antifungal activity against Malassezia yeasts in vitro and exhibited comparable efficacy to itraconazole in treating MF patients. Without the associated adverse effects of oral antifungal drugs, CAP can be considered a promising and safe treatment modality for MF.

Extracellular phospholipase production by Malassezia pachydermatis strains and its inhibition by selected antimycotics and plant essential oil components

Extracellular phospholipase (EPL) plays an important role in the pathogenesis of the yeast Malassezia pachydermatis. Currently, the attention of researchers is focused on studying the virulence factors involved in this process and searching solutions to reduce their activity. One of the options is the use of natural remedies as anti-virulence agents. This study is aimed at investigating the production of extracellular phospholipase in M. pachydermatis strains (18 samples) and followed by the time-dependent inhibitory effect of selected azole antifungals (itraconazole, posaconazole and voriconazole) and plant essential oil components (terpinen-4-ol, thymol, carvacrol, eugenol and geraniol), evaluated by Egg Yolk Agar plate method. Almost all strains (17 isolates, (94.4%) were found to be intense EPL producers. A significant, time-dependent inhibition of EPL was noted after 1-, 3- and 6-h exposure of Malassezia cells to itraconazole (26.4%, 47.2% and 50.9%, respectively) compared to exposure to posaconazole (26.4%, 28.3% and 28.3%, respectively) and voriconazole (18.8%, 20.8% and 35.8%, respectively). After one-hour exposure to plant essential oil components, the best inhibitory effect was recorded for eugenol (62.3%), followed by terpinen-4-ol and thymol (56.6%), geraniol (41.5%) and carvacrol (26.4%). A 3-h exposure revealed that thymol retained the best inhibitory effect (88.7%) on EPL production, followed by carvacrol (73.6%), eugenol (56.6%), terpinen-4-ol (52.8%) and geraniol (49.1%). After 6-h exposure, no growth of M. pachydermatis strains exposed to carvacrol was observed, and the inhibitory efficiency for the other tested essential oil (EO) components achieved 88.7%. The obtained results indicate the promising efficacy of plant essential oils components in the inhibition of virulence factors such as EPL production.

COMPREHENSIVE STUDY ON PONGAMIA GLABRA VENT. SEED OIL: EXTRACTION, CHARACTERIZATION, AND ANTIFUNGAL ACTIVITY ASSESSMENT

Dandruff remains a prevalent issue globally, impacting individuals across diverse demographics. Its manifestation, characterized by the shedding of scalp skin cells leading to visible flakes, presents in dry and oily forms, each with distinct attributes. While the prevalence peaks during puberty, various factors such as humidity, trauma, and stress exacerbate symptoms. Malassezia yeast overgrowth, thriving in sebum-rich areas, plays a pivotal role, with environmental triggers further complicating the condition. Addressing dandruff necessitates multifaceted approaches, including understanding its pathophysiology and exploring diverse treatment modalities. This study focuses on Pongamia glabra Vent. seed oil, commonly known as karanj oil, extracted via a comprehensive methodology involving hydrodistillation and cold expression techniques. Characterization of the oil revealed specific properties, including appearance, odor, taste, solubility, and specific gravity, essential for evaluating its quality and suitability for various applications. Additionally, screening for antifungal activity against Malassezia furfur demonstrated promising results, with karanj oil exhibiting significant efficacy, highlighting its potential as a natural alternative for combating fungal infections associated with dandruff.

Otitis externa in dogs (prevalence, etiology, clinical course, and treatment regimens)

Otitis externa is a reasonably common problem in dogs. The most difficult is the treatment of recurrent chronic otitis media. After all, otitis externa in dogs is a polyetiological disease; therefore, to prescribe effective treatment, the doctor needs to identify the primary cause and take it under control, as well as identify and eliminate secondary infections and develop a prevention plan following predisposing factors. That is why a detailed analysis of the scientific literature on the distribution, etiology, clinical course, and scheme of treatment of dogs with the development of otitis externa was made. To ensure the accuracy and speed of diagnosis of otitis externa, it is promising to develop a diagnostic algorithm that will help the general practitioner clearly understand the etiological factors and eliminate them or take them under control. Many researchers have confirmed that otitis is characterized by seasonality (18.6 % occurs in summer, 30.2 % in autumn, 15.6 % in winter, and 35.6 % in spring). Depending on otitis's etiology in small domestic animals, microorganisms, fungi, and mites are decisive. According to the reports of some authors, otitis externa can be secondary; that is, the etiology of such pathology is already an infection (Staphylococcus and Pseudomonas bacteria, Malassezia yeast). Clinically, otitis externa in dogs, as a rule, is manifested by characteristic symptoms, while the existing peculiarities of the course are, in most cases, determined by etiological factors. In most cases, otitis externa is treated locally with drugs applied directly to the ear. Most of these products contain different ingredients that are active against bacteria, yeast, and inflammation at the same time. There are several remedies for the treatment of otitis externa at the veterinarian's choice, which require different treatment regimens. Recently, the practice of veterinary medicine has increasingly included complex drugs that, on the one hand, are effective in the treatment of otitis and, on the other hand, are safe for the animal body. Such drugs, as a rule, should show, at the same time, anti-inflammatory, anti-parasitic, anti-allergic, analgesic, immunomodulating, and other types of action. Because of this, the search and development of new drugs in the system of comprehensive measures for the prevention and treatment of inflammation of the external ear is relevant and promising.

Whole-Genome Shotgun Metagenomic Sequencing Reveals Shifts in the Skin Microbiome and Bacteriophages of Psoriasis: An Extended Analysis of Published Data

Background Psoriasis is an immune-mediated cutaneous disease that may have shifts in the skin microbiome. Prior research on the skin microbiome in psoriasis has been limited to rRNA based approaches that lack resolution of taxonomic and functional level assessment. Objective To further illuminate strain and sub-strain level analysis of psoriatic lesions using the CosmosID-HUB Microbiome pipeline. Methods A previous study completed by Tett et al recruited patients with psoriasis who had skin microbiome samples taken from psoriatic plaques on the ear and the elbow as well as sites on the skin unaffected by psoriasis. They performed whole genome shotgun sequencing and made their dataset publicly available. We analyzed the dataset using the CosmosID-HUB Microbiome pipeline to evaluate the strain and sub-strain taxonomic analysis as well as functional gene profiling. Results When analyzed with the CosmosID pipeline, both ear and elbow sites in affected areas had decreased alpha diversity compared to unaffected areas. There was an increased relative abundance of Staphylococcus and Corynebacteria at affected sites. We identified distinguishing species and strains of the yeast Malassezia, including M. restricta. that were significantly enriched in healthy elbow samples. Vitamin B12 production genes were not present in psoriatic skin whereas it was present in healthy samples, supporting the notion of relative vitamin B12 deficiency in psoriatic plaques. Phage analysis revealed a greater diversity of Staphylococcus-related phages in unaffected elbow samples. Conclusion A greater diversity of microbial strains and their functional roles identified in this study may help to tailor treatment for psoriasis.

Efficacy of Combination of Topical Ketoconazole 2% Cream and Adapalene 0.1% Gel versus Topical Ketoconazole 2% Cream Alone in Treatment of Pityriasis Versicolor

Pityriasis Versicolor (PV) is a superficial skin infection caused by Malassezia yeasts, resulting in hypo and hyperpigmented macules. It affects up to 40% of individuals, often leading to itching, decreased quality of life, and social stigma. Objective: To compare the efficacy of combination of topical ketoconazole 2% cream and adapalene 0.1% gel versus topical ketoconazole 2% cream alone in treatment of pityriasis versicolor. Methods: A comparative cross-sectional study was conducted at the Department of Dermatology, Nishtar Hospital, Multan, spanning from November 2020 to April 2021. Total 90 patients were divided equally into two groups: Group A received a combination of Ketoconazole 2% cream and adapalene 1% gel, while Group B received Ketoconazole 2% cream alone. The efficacy of both treatments was evaluated and compared. The study utilized SPSS version 26.0 for data analysis. Results: In terms of gender, 52.22% were male, and 47.78% were female across both groups. The mean duration of the disease was 5.84 ± 3.26 years in Group A and 6.04 ± 3.11 years in Group B, with an overall mean of 5.95 ± 3.17 years. The efficacy of Group A was 91.11%, with 41 participants showing positive results, while Group B had an efficacy of 75.56%, with 34 participants showing positive results. Conclusions: The study findings indicate that using a combination of adapalene 0.1% gel and ketoconazole 2% cream is more efficacious than using ketoconazole 2% cream alone in treating PV

Mycobiome of the external ear canal of healthy cows.

Malassezia yeasts belong to the normal skin microbiota of a wide range of warm-blooded animals. However, their significance in cattle is still poorly understood. In the present study, the mycobiota of the external ear canal of 20 healthy dairy Holstein cows was assessed by cytology, culture, PCR, and next-generation sequencing. The presence of Malassezia was detected in 15 cows by cytology and PCR. The metagenomic analysis revealed that Ascomycota was the predominant phylum but M. pachydermatis the main species. The Malassezia phylotype 131 was detected in low abundance. Nor M. nana nor M. equina were detected in the samples.

Water-filtered infrared A irradiation exerts antifungal effects on the skin fungus Malassezia

Many common skin diseases are associated with changes in the microbiota. This applies for the commensal yeast Malassezia, which is linked to a wide range of skin disorders ranging from mild dandruff to severe seborrheic and atopic dermatitis, all of which have a detrimental impact on the individuals' quality of life. While antifungal medications offer relief in many cases, the challenges of disease recurrence and the emergence of resistance to the limited range of available antifungal drugs poses a pressing need for innovative therapeutic options. Here we examined the activity of water-filtered infrared A (wIRA) irradiation against Malassezia. wIRA's antimicrobial and wound healing properties make it an attractive option for localized, non-invasive, and contact-free treatment of superficial skin infections. Irradiation of Malassezia furfur with wIRA (570–1400 nm) resulted in a reduction of the yeast's metabolic activity. When put in contact with immune cells, wIRA-irradiated M. furfur was recovered at lower counts than non-irradiated M. furfur. Likewise, wIRA irradiation of M. furfur put in contact with keratinocytes, the primary host interface of the fungus in the skin, reduced the fungal counts, while the keratinocytes were not affected by the irradiation. The combination of wIRA with the photosensitizer methyl aminolevulinate exerted an additional antifungal effect on M. furfur, irrespective of the presence or absence of keratinocytes, suggesting an enhancement of the treatment effect when used in combination. These findings suggest that wIRA holds promise as a potential therapy for skin disorders associated with Malassezia.

Phylogenetic analyses reveal insights into interdomain horizontal gene transfer of microbial lipases

Microbial lipases play a pivotal role in a wide range of biotechnological processes and in the human skin microbiome. However, their evolution remains poorly understood. Accessing the evolutionary process of lipases could contribute to future applications in health and biotechnology. We investigated genetic events associated with the evolutionary trajectory of the microbial family LIP lipases. Using phylogenetic analysis, we identified two distinct horizontal gene transfer (HGT) events from Bacteria to Fungi. Further analysis of human cutaneous mycobiome members such as the lipophilic Malassezia yeasts and CUG-Ser-1 clade (including Candida sp. and other microorganisms associated with cutaneous mycobiota) revealed recent evolutionary processes, with multiple gene duplication events. The Lid region of fungal lipases, crucial for substrate interaction, exhibits varying degrees of conservation among different groups. Our findings suggest the adaptability of the fungal LIP family in various genetic and metabolic contexts and its potential role in niche exploration.

More yeast, more problems?: reevaluating the role of Malassezia in seborrheic dermatitis.

Seborrheic dermatitis (SD) is an inflammatory skin disorder and eczema subtype increasingly recognized to be associated with significant physical, psychosocial, and financial burden. The full spectrum of SD, including dandruff localized to the scalp, is estimated to affect half of the world's population. Despite such high prevalence, the exact etiopathogenesis of SD remains unclear. Historically, many researchers have theorized a central, causative role of Malassezia spp. based on prior studies including the proliferation of Malassezia yeast on lesional skin of some SD patients and empiric clinical response to antifungal therapy. However, upon closer examination, many of these findings have not been reproducible nor consistent. Emerging data from novel, targeted anti-inflammatory therapeutics, as well as evidence from genome-wide association studies and murine models, should prompt a reevaluation of the popular yeast-centered hypothesis. Here, through focused review of the literature, including laboratory studies, clinical trials, and expert consensus, we examine and synthesize the data arguing for and against a primary role for Malassezia in SD. We propose an expansion of SD pathogenesis and suggest reframing our view of SD to be based primarily on dysregulation of the host immune system and skin epidermal barrier, like other eczemas.

Non-invasive evaluation of cytokine expression using the cerumen of dogs with otitis externa.

The development of a non-invasive method to analyze cytokine expression in the skin will provide further understanding of inflammatory skin disorders. This study aimed to evaluate cytokine expression in the skin through cerumen swabbing in dogs with otitis externa (OE) and to investigate whether increased cytokine expression in infected OE reflects the inflammatory status of the ear canal. Three groups consisting of control dogs (n = 24), dogs with ceruminous Malassezia OE (n = 25), and dogs with suppurative bacterial OE (n = 15) were included in the study. The concentrations of keratinocyte-derived cytokines including Interleukin (IL)-8/chemokine ligand (CXCL)8, IL-10, IL-6, Tumor necrosis factor (TNF)-α, and IL-1ß in the cerumen of the ear canal of the included patients were analyzed using commercial ELISA kits. Additionally, correlations between cytokine levels and cytology scores (of Malassezia yeasts, cocci/rod-shaped bacteria, and inflammatory cells) were assessed. IL-8/CXCL8 concentrations were significantly higher in dogs with ceruminous Malassezia OE and dogs with suppurative bacterial OE than in control dogs. Furthermore, IL-8/CXCL8 concentrations positively correlated with Malassezia scores in dogs with ceruminous OE (r = 0.630) and with bacterial scores in dogs with suppurative OE (r = 0.601). In addition, increased expression of IL-6 and IL-1ß were detected in dogs with suppurative bacterial OE compared to those with Malassezia OE and control dogs, and showed positive correlation with inflammatory cell scores IL-6 r = 0.520, IL-1ß; r = 0.680). Therefore, keratinocyte-derived cytokines could be evaluated using non-invasive methods such as cerumen swabbing in dogs with OE.

Epidermal barrier impairment predisposes for excessive growth of the allergy-associated yeast Malassezia on murine skin.

The skin barrier is vital for protection against environmental threats including insults caused by skin-resident microbes. Dysregulation of this barrier is a hallmark of atopic dermatitis (AD) and ichthyosis, with variable consequences for host immune control of colonizing commensals and opportunistic pathogens. While Malassezia is the most abundant commensal fungus of the skin, little is known about the host control of this fungus in inflammatory skin diseases. In this experimental study, MC903-treated mice were colonized with Malassezia spp. to assess the host-fungal interactions in atopic dermatitis. Additional murine models of AD and ichthyosis, including tape stripping, K5-Nrf2 overexpression and flaky tail mice, were employed to confirm and expand the findings. Skin fungal counts were enumerated. High parameter flow cytometry was used to characterize the antifungal response in the AD-like skin. Structural and functional alterations in the skin barrier were determined by histology and transcriptomics of bulk skin. Finally, differential expression of metabolic genes in Malassezia in atopic and control skin was quantified. Malassezia grows excessively in AD-like skin. Fungal overgrowth could, however, not be explained by the altered immune status of the atopic skin. Instead, we found that by upregulating key metabolic genes in the altered cutaneous niche, Malassezia acquired enhanced fitness to efficiently colonise the impaired skin barrier. This study provides evidence that structural and metabolic changes in the dysfunctional epidermal barrier environment provide increased accessibility and an altered lipid profile, to which the lipid-dependent yeast adapts for enhanced nutrient assimilation. Our findings reveal fundamental insights into the implication of the mycobiota in the pathogenesis of common skin barrier disorders.