Malassezia Research Articles

Malassezia Is Associated with Crohn’s Disease and Exacerbates Colitis in Mouse Models

Inflammatory bowel disease (IBD) is characterized by alterations in the intestinal microbiota and altered immuneresponses to gut microbiota. Evidence is accumulating that IBD is influenced by not only commensal bacteria but also commensal fungi. We characterized fungi directly associated with the intestinalmucosa in healthy people and Crohn's disease patients and identified fungi specifically abundant in patients. One of these, the common skin resident fungus Malassezia restricta, is also linked to the presence of an IBD-associated polymorphism in the gene for CARD9, a signaling adaptor important for anti-fungal defense. M.restricta elicits innate inflammatory responses largely through CARD9 and is recognized by Crohn's disease patient anti-fungal antibodies. This yeast elicits strong inflammatory cytokine production from innate cells harboring the IBD-linked polymorphism in CARD9 and exacerbates colitis via CARD9 in mouse models of disease. Collectively, these results suggest that targeting specific commensal fungi may be a therapeutic strategy for IBD.

Identification and Evaluation of Inhibitors of Lipase from Malassezia restricta using Virtual High-Throughput Screening and Molecular Dynamics Studies

Recent studies revealed the role of lipase in the pathogenicity of Malassezia restricta in dandruff and seborrheic dermatitis (D/SD). The lipase from M. restricta (Mrlip1) is considered a potential target for dandruff therapy. In this work, we performed structure-based virtual screening in Zinc database to find the natural bioactive inhibitors of Mrlip1. We identified three compounds bearing superior affinity and specificity from the Traditional Chinese Medicine database (~60,000 compounds), and their binding patterns with Mrlip1 were analyzed in detail. Additionally, we performed three sets of 100 ns MD simulations of each complex in order to understand the interaction mechanism of Mrlip1 with known inhibitor RHC80267 and the newly identified compounds such as ZINC85530919, ZINC95914464 and ZINC85530320, respectively. These compounds bind to the active site cavity and cause conformational changes in Mrlip1. The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) studies suggested that the average binding energy was stronger in the case of Mrlip1-ZINC85530919 and Mrlip1-ZINC95914464. The selected natural inhibitors might act as promising lead drugs against Mrlip1. Further, the present study will contribute to various steps involved in developing and creating potent drugs for several skin diseases including dandruff.

Complete Genome Sequence of Malassezia restricta CBS 7877, an Opportunist Pathogen Involved in Dandruff and Seborrheic Dermatitis.

Malassezia restricta, one of the predominant basidiomycetous yeasts present on human skin, is involved in scalp disorders. Here, we report the complete genome sequence of the lipophilic Malassezia restricta CBS 7877 strain, which will facilitate the study of the mechanisms underlying its commensal and pathogenic roles within the skin microbiome.

Inhibition of α-, β-, γ-, δ-, ζ- and η-class carbonic anhydrases from bacteria, fungi, algae, diatoms and protozoans with famotidine

Famotidine, an antiulcer drug belonging to the H2 antagonists class of pharmacological agents, was recently shown to potently inhibit human (h) and bacterial carbonic anhydrases (CAs, EC 4.2.1.1). We investigated the inhibitory effects of famotidine against all classes of CAs from the pathogenic bacteria Vibrio cholerae, Burkholderia pseudomallei and Mycobacterium tuberculosis Rv3273 β-CA, as well as the CAs from the nonpathogenic bacteria/cyanobacteria Sulfurihydrogenibium yellowstonensis, S. azorense, Pseudoalteromonas haloplanktis, Colwellia psychrerythraea and Nostoc commune. The δ- and ζ-CAs from the diatom Thalassiosira weissflogii, the fungal enzymes from Cryptococcus neoformans, Candida glabrata and Malassezia globosa, as well as the protozoan enzymes from Trypanosoma cruzi and Plasmodium falciparum, were also investigated. Anopheles gambiae β-CA was also investigated. All these enzymes were effectively inhibited by famotidine, with affinities between the low nanomolar to the micromolar range. The best inhibition was observed against C. glabrata β-CA and TweCAζ, with KIs ranging between 13.6 and 22.1 nM.

Molecular Characterization of Malassezia spp Isolated from Human Pityriasis Versicolor

The study was looking to isolation and identification of various species of Malassezia isolates associated with various clinical phenomena of pityriasis versicolor by molecular Techniques the results of DNA extraction showed that most of the isolates give just single bundle of DNA on agarose gel, and according to PCR results, thirteen DNA samples (43.3%) were amplified after PCR program for amplification by two sets of primers ITS1-ITS4 3.2 and V9G-LS266, then all the thirteen isolates were subjected to DNA sequencing which showed the following results: eight isolates identified as Malassezia furfur and five as Malassezia globosa with the alignment bellow of each species. Malassezia furfur isolate POL.10.11. IIIA 18S ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and 28S ribosomal RNA gene, partial sequence. Sequence ID: KC152898.1 Length: 848 Number of Matches: 1Range 1: 1 to 848. Phylogenetic analysis of the 13 Malassezia isolates were analyzed by MEGA 5.05 and compared with sequences of different Malassezia species available in Gen Bank database, the data showed a clear convergence between our Malassezia isolates from Basra patients and that of the Gen Bank database.

MGL_3741 gene contributes to pathogenicity of Malassezia globosa in pityriasis versicolor.

Dihydroxyacid dehydratase (DHAD) is a key enzyme in biosynthetic pathway of isoleucine and valine. This pathway is absent in human but exists in various organisms such as fungi. Using RNA-seq analysis in this study, we identified MGL_3741gene which encodes DHAD protein in Malassezia globosa (M.globosa). Furthermore, we found that mentioned gene is homologous to the Ustilago maydis, Saccharomyces cerevisiae, Aspergillus flavus, and Aspergillus fumigatus ILV3P. For understanding the probable role of this gene in pathogenicity of M.globosa, we applied Real-time PCR to investigate the differentially expressed of the MGL_3741 gene in healthy and pathogenic states. Our results indicate a significant difference between two mentioned stats. These results revealed that ILV3-like gene in M.globosa can be related to the pathogenicity of this yeast.

The oral microbiome in oral lichen planus during a 1-year randomized clinical trial.

Several recent studies have investigated the oral bacteriome in oral lichen planus (OLP), but longitudinal changes in microbiome have not been investigated. To study the bacteriome and mycobiome in OLP over a 1-year period and the impact of topical treatment. Samples from 22 symptomatic OLP patients from a double-blinded, randomized intervention study were collected over a 1-year course at five visits. Bacterial and fungal abundances were investigated through lesional cytobrush (CB) and full mouthwash (MW). Initially, all patients received conventional (antimycotic or steroid) and probiotic or placebo treatment. The microbial composition differed between the MW and CB samples. During the study period, the microbial composition was individual, with pronounced variability between visits. Patients grouped according to initial conventional treatment. During the study period, unidirectional change in the bacteriome was seen in the antimycotic group, whereas the mycobiome was stable. Malassezia restricta was the most abundant fungus. The microbial composition of MW and CB differs in OLP. CB composition is less influenced by conventional and probiotic intervention. Initial antimycotic treatment influenced the bacteriome during the 1-year period. How the oral microbiome in health and disease is influenced by individual variability of fungi and bacteria, and Malassezia needs further investigation.

Understanding the Mechanism of Action of the Anti-Dandruff Agent Zinc Pyrithione against Malassezia restricta

Dandruff is known to be associated with Malassezia restricta. Zinc pyrithione (ZPT) has been used as an ingredient in anti-dandruff treatments. The mechanism of ZPT has been investigated in several studies; however, a non-pathogenic model yeast, such as Saccharomyces cerevisiae was most often used. The aim of the present study was to understand how ZPT inhibits the growth of M. restricta. We analyzed the cellular metal content and transcriptome profile of ZPT-treated M. restricta cells and found that ZPT treatment dramatically increased cellular zinc levels, along with a small increase in cellular copper levels. Moreover, our transcriptome analysis showed that ZPT inhibits Fe-S cluster synthesis in M. restricta. We also observed that ZPT treatment significantly reduced the expression of lipases, whose activities contribute to the survival and virulence of M. restricta on human skin. Therefore, the results of our study suggest that at least three inhibitory mechanisms are associated with the action of ZPT against M. restricta: (i) an increase in cellular zinc levels, (ii) inhibition of mitochondrial function, and (iii) a decrease in lipase expression.

Combined Spinal Epidural in a Parturient With Tinea Versicolor

(J Clin Anesth. 2017;43:63–64) In this correspondence, the authors discussed the case of a 33-year-old parturient who presented for labor analgesia (combined spinal epidural technique) with a history of recurrent lumbar tinea versicolor, as well as a maculopapular rash from the cervical to the sacral area on physical examination. Tinea versicolor is a benign condition in which Malassezia globosa, a yeast found in normal flora, becomes pathogenic following exposure to heat and humidity in immunosuppressed individuals. Following informed consent, combined spinal epidural labor analgesia was administered with a 27-G Pencan spinal needle following sterile skin preparation and using a needle-through-needle technique. The epidural catheter remained in situ for 13 hours. The authors reported an uneventful delivery and postoperative course.

Benzamide-4-Sulfonamides Are Effective Human Carbonic Anhydrase I, II, VII, and IX Inhibitors.

A series of benzamides incorporating 4-sulfamoyl moieties were obtained by reacting 4-sulfamoyl benzoic acid with primary and secondary amines and amino acids. These sulfonamides were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The human (h) isoforms hCA II, VII, and IX were inhibited in the low nanomolar or subnanomolar ranges, whereas hCA I was slightly less sensitive to inhibition (KIs of 5.3–334 nM). The β- and γ-class CAs from pathogenic bacteria and fungi, such as Vibrio cholerae and Malassezia globosa, were inhibited in the micromolar range by the sulfonamides reported in the paper. The benzamide-4-sulfonamides are a promising class of highly effective CA inhibitors.

Comparison of Selenium Sulfide 1% and Zinc Pyrithione 1% and Combination of them in Overcoming Malassezia Globosa in Vitro

Comparison of Selenium Sulfide 1% and Zinc Pyrithione 1% and Combination of them in Overcoming Malassezia Globosa in Vitro

The Skin Commensal Yeast Malassezia globosa Thwarts Bacterial Biofilms to Benefit the Host

Malassezia are abundant, lipid-dependent, commensal yeasts in the skin microbiome that also have a pathogenic lifestyle associated with several common skin disorders. Malassezia genomes encode myriad lipases and proteases thought to mediate lipid utilization and pathogenesis. Li etal. report the biochemical characterization of a unique secreted aspartyl protease produced by Malassezia globosa, MgSAP1, and demonstrate its active role in hindering biofilm formation of the bacterium Staphylococcus aureus. Because biofilms are an established virulence attribute of S.aureus, this study reveals a potential benefit to the host of the fungal aspartyl protease MgSAP1 and opens the door for the investigation of the roles of such molecules in microbial interactions and their possible effects on the host.

Epidemiological profile of cutaneous superficial mycoses in South, Brazil

Cutaneous superficial mycoses appear as lesions on the skin, hair and nails. The highest prevalence is of fungal infections caused by the fungi of the genus Microsporum , Epidermophyton , Trichophyton , Candida and Malassezia . These mycoses are common in tropical regions and are commonly neglected due to lack of patient knowledge, difficult diagnosis and lack of access to health facilities, which makes them a public health problem. In research, mycological examination of patients using Basic Health Units (BHU) was carried out in order to diagnose mycoses. Through this action, it was possible to diagnose and refer to the appropriate treatment 5359 patients, seeking to improve their quality of life. From the results of the mycological exams of these patients during the period from 2011 to 2016, it was possible to trace the epidemiological profile of the State of Rio Grande do Sul and the most prevalent species, contributing to the accomplishment of measures in public health.

Natural Polyphenols Selectively Inhibit β-Carbonic Anhydrase from the Dandruff-Producing Fungus Malassezia globosa: Activity and Modeling Studies.

Around 50 % of the worldwide population is affected by dandruff, which is triggered by a variety of factors. The yeast Malassezia globosa has been labeled as the most probable causative agent for the onset of dandruff. The β-carbonic anhydrase (CA) of MgCA was recently validated as an anti-dandruff target, with its inhibition being responsible for in vivo growth defects in the fungus. As classical CA inhibitors of the sulfonamide type give rise to permeability problems through biological membranes, finding non-sulfonamide alternatives for MgCA inhibition is of considerable interest in the cosmetic field. We recently screened a large library of human (h) CA inhibitors for MgCA inhibition, including different chemotypes, such as monothiocarbamates, dithiocarbamates, phenols, and benzoxaboroles. Herein, we expanded the research toward new MgCA inhibitors by considering a set of natural polyphenols (including flavones, flavonols, flavanones, flavanols, isoflavones, and depsides) that exhibited MgCA inhibitory activity in the micromolar range, as well as selectivity for the fungal isozyme over off-target human isoforms. The binding mode of representative derivatives within the MgCA catalytic cleft was investigated by docking studies using a homology-built model.

Analysis of the skin mycobiome in adult patients with atopic dermatitis.

With the recent availability of culture-independent sequencing methods, studies have been conducted to analyse skin micro-organisms present in patients with atopic dermatitis (AD). However, the database on the skin fungal communities, "mycobiome," has been relatively restrictive compared with the bacterial world. We aimed to comparatively analyse the overall skin mycobiome between patients with AD and healthy individuals in the Korean population. We analysed skin swab samples obtained from the antecubital fossae of 8 patients with AD and 8 healthy controls. Using sequencing method followed by direct DNA extraction and molecular PCR, taxonomic compositions of fungi at stepwise level ranks were analysed. The phylogenic marker used was internal transcribed spacer 2 regions of DNA. We observed the tendency of higher intra- and interpersonal taxonomic diversity at genus and species levels in AD samples. Non-Malassezia fungal diversity was also noticeable in the patient group compared with healthy controls. Malassezia globosa and Malassezia restricta were prevalent in all samples across both study groups, and some Malassezia species, including Malassezia sloofiae and Malassezia dermatis, characterized AD. Our data might provide a new insight into the mycobiome of adult AD, which contributes to building a systemic mycobiome database in AD.

Metabarcoding analysis of eukaryotic microbiota in the gut of HIV-infected patients.

Research on the relationship between changes in the gut microbiota and human disease, including AIDS, is a growing field. However, studies on the eukaryotic component of the intestinal microbiota have just begun and have not yet been conducted in HIV-infected patients. Moreover, eukaryotic community profiling is influenced by the use of different methodologies at each step of culture-independent techniques. Herein, initially, four DNA extraction protocols were compared to test the efficiency of each method in recovering eukaryotic DNA from fecal samples. Our results revealed that recovering eukaryotic components from fecal samples differs significantly among DNA extraction methods. Subsequently, the composition of the intestinal eukaryotic microbiota was evaluated in HIV-infected patients and healthy volunteers through clone sequencing, high-throughput sequencing of nuclear ribosomal internal transcribed spacers 1 (ITS1) and 2 (ITS2) amplicons and real-time PCRs. Our results revealed that not only richness (Chao-1 index) and alpha diversity (Shannon diversity) differ between HIV-infected patients and healthy volunteers, depending on the molecular strategy used, but also the global eukaryotic community composition, with little overlapping taxa found between techniques. Moreover, our results based on cloning libraries and ITS1/ITS2 metabarcoding sequencing showed significant differences in fungal composition between HIV-infected patients and healthy volunteers, but without distinct clusters separating the two groups. Malassezia restricta was significantly more prevalent in fecal samples of HIV-infected patients, according to cloning libraries, whereas operational taxonomic units (OTUs) belonging to Candida albicans and Candida tropicalis were significantly more abundant in fecal samples of HIV-infected patients compared to healthy subjects in both ITS subregions. Finally, real-time PCR showed the presence of Microsporidia, Giardia lamblia, Blastocystis and Hymenolepis diminuta in different proportions in fecal samples from HIV patients as compared to healthy individuals. Our work revealed that the use of different sequencing approaches can impact the perceived eukaryotic diversity results of the human gut. We also provide a more comprehensive view of the eukaryotic community in the gut of HIV-infected patients through the complementarity of the different molecular techniques used. Combining these various methodologies may provide a gold standard for a more complete characterization of the eukaryotic microbiome in future studies.

Clinical profile of patients with tinea versicolor

<p class="abstract"><strong>Background:</strong> <span lang="EN-IN">Pityriasis versicolor is a superficial fungal infection caused by the polymorphous endogenous yeast <em>Malassezia furfur</em>. Infection typically occurs on the trunk and proximal upper extremities and is characterized by distinctive scaly, coalescent hyperpigmented and/or hypopigmented to erythematous patches. Tinea versicolor is a superficial chronically recurring fungal infection of the stratum corneum, characterized by scaly, hypo and hyperpigmented irregular macules, usually located on the trunk and proximal extremities caused by pityrosporum orbiculare.</span></p><p class="abstract"><strong>Methods:</strong> <span lang="EN-IN">100 patients of untreated tinea versicolor who attended the outpatient department were selected at random irrespective of their age, socioeconomic status, occupation. A detailed history was taken, regarding the age, sex, religion, occupation, socioeconomic status, residence, duration and course of the disease, site of distribution of lesion and any other associated cutaneous and systemic diseases</span>.<strong></strong></p><p class="abstract"><strong>Results:</strong> <span lang="EN-IN">The majority patients i.e. 27 (27%) were students and followed by the unskilled workers who comprised 20% of patients. The incidence is quite low in business and official class 3% and 11% respectively. </span></p><p class="abstract"><strong>Conclusions:</strong> <span lang="EN-IN">The duration of the disease in 93% of patients was less than 10 years and in 7% the duration was more than 10 years.</span></p>

Inhibitory effect of plant essential oils on Malassezia strains from Iranian dermatitis patients

Introduction: The genus Malassezia is an important skin resident of human. The present study aimed to analyze in vitro activity of the essential oils of Lavandula stoechas, Cuminum cyminum and Artemisia sieberi against clinical strains of Malassezia species.Methods: A total of 47 Malassezia strains, including Malassezia furfur, Malassezia globosa and Malassezia obtuse, were used in this study. A disk diffusion technique was selected for testing the susceptibility of Malassezia strains to the essential oils.Results: All the essential oils showed in vitro activity against Malassezia strains, with M. furfur and M. obtusa being the highest and lowest susceptible of the strains, respectively. The highest antifungal activity was associated with the essential oil of C. cyminum (mean ± SD: 50.0 ± 0.0 mm), followed by L. stoechas (mean ± SD: 46.8 ± 3.1 mm) and A. sieberi (mean ± SD: 36.9 ± 5.7 mm). The inhibition zone ranges were 12.5 to 15.6 mm (mean ± SD: 14.4 ± 1.6 mm) for ketoconazole and 11.6 to 13.3 mm (mean ± SD: 12.4 ± 0.9 mm) for fluconazole. Although all the antifungal drugs were found to possess good antifungal activities against Malassezia strains, their effects were lower than the activities shown by the essential oils tested (P < 0.05).Conclusion: These results indicated that the essential oils tested, especially the one from C. cyminum, inhibited the growth of clinical strains of Malassezia, implying its potential use in the treatment of Malassezia infections. This indicates that this plant may be useful in preparation of new drugs.

Fungal Diversity in Gut Microbiota in Patients with Cancer

Patients who have cancer are more prone to get infections than healthy individuals. In this study, we applied cloning sequencing technique to identify the mycobiome and other transient fungal components in the digestive tract of patients with acute myeloid leukemia (AML), non- Hodgkin’s lymphoma (NHL), Leucopenia and anemia and compare it with the fungal components of healthy individuals. Fungal universal primer pair targeting ITS region of the fungal genome was used to assess the fungal components in fecal samples. Approximately more than 1,481 clones were selected and subjected to sequence analysis resulted in detection of a total of 44 and 43 fungal species from both fecal samples of cancer patients and healthy control individuals respectively. The majority of fungi were assigned to the 3 taxa Ascomycota (n = 39/63, 61.9 %), Basidiomycota (n = 23/63, 36.5 %) and Zygomycota (n= 1/63, 1.6 %). Fungal species such as Candida parapsilosis , Candida dubliniensis , Malassezia restricta were represented only in the feces of cancer patients. Moreover, the results from analyzing ITS clone library revealed that the most frequently detected fungi of the Malassezia genus ( Malassezia globosa , Malassezia pachydermatis , Malassezia restricta ) were retrieved in high amount in the fecal samples of cancer patients compared with those of healthy volunteers. Further efforts and studies are needed to shed light on the complex relationships between the fungal populations and the host immune system in cancer patients.

Skin Commensal Malassezia globosa Secreted Protease Attenuates Staphylococcus aureus Biofilm Formation

Skin provides the first defense against pathogenic micro-organisms and is also colonized by a diverse microbiota. Phylogenetic analysis of whole skin microbiome at different skin sites in health and disease has generated important insights on possible microbial involvement in modulating skin health. However, functional roles of the skin microbial community remain unclear. The most common sebaceous skin commensal yeasts are the basidiomycetes, Malassezia. Here, we characterized the dominant secreted Malassezia globosa protease in culture and subsequently named it Malassezia globosa Secreted Aspartyl Protease 1 (MgSAP1). We defined recombinant MgSAP1's substrate cleavage profile using an unbiased, mass-spectrometry-based technique. We show that this enzyme is physiologically relevant as mgsap1 expression was detected on at least one facial skin site of 17 healthy human volunteers. In addition, we demonstrated that this protease rapidly hydrolyzes Staphylococcus aureus protein A, an important S.aureus virulence factor involved in immune evasion and biofilm formation. We further observed that MgSAP1 has anti-biofilm properties against S.aureus. Taken together, our study defines a role for the skin fungus Malassezia in inter-kingdom interactions and suggests that this fungus and the enzymes it produces may be beneficial for skin health.