Targeted Delivery of Zinc Pyrithione to Skin Epithelia

Zinc pyrithione (ZnPT) is an anti-fungal drug delivered as a microparticle to skin epithelia. It is one of the most widely used ingredients worldwide in medicated shampoo for treating dandruff and seborrheic dermatitis (SD), a disorder with symptoms that include skin flaking, erythema and pruritus. SD is a multi-factorial disease driven by microbiol dysbiosis, primarily involving Malassezia yeast. Anti-fungal activity of ZnPT depends on the cutaneous availability of bioactive monomeric molecular species, occurring upon particle dissolution. The success of ZnPT as a topical therapeutic is underscored by the way it balances treatment efficacy with formulation safety. This review demonstrates how ZnPT achieves this balance, by integrating the current understanding of SD pathogenesis with an up-to-date analysis of ZnPT pharmacology, therapeutics and toxicology. ZnPT has anti-fungal activity with an average in vitro minimum inhibitory concentration of 10–15 ppm against the most abundant scalp skin Malassezia species (Malassezia globosa and Malassezia restrica). Efficacy is dependent on the targeted delivery of ZnPT to the skin sites where these yeasts reside, including the scalp surface and hair follicle infundibulum. Imaging and quantitative analysis tools have been fundamental for critically evaluating the therapeutic performance and safety of topical ZnPT formulations. Toxicologic investigations have focused on understanding the risk of local and systemic adverse effects following exposure from percutaneous penetration. Future research is expected to yield further advances in ZnPT formulations for SD and also include re-purposing towards a range of other dermatologic applications, which is likely to have significant clinical impact.

GC-MS Analysis and Molecular Docking Studies of Active Phytochemicals from Medicinal Plants against Malassezia Globosa LIP1 (SMG1) Enzyme

Malassezia globosa LIP1 (SMG1) lipase plays a crucial role in the pathogenicity of M. globosa in dandruff sufferers. In this study, GC-MS analysis of selected medicinal plants was done, and antifungal activity of these identified phytochemicals was checked by molecular docking method against Malassezia globosa LIP1 (SMG1) lipase using AutoDock 4.0. SwissADME tool was used to analyze the absorption, distribution, metabolism, excretion (ADME) of phytoligands. GC-MS showed various phytoconstituents in the Glycyrrhiza glabra extract, including glabridin, 2-propenal, 3-phenyl-eugenol, 4'-O-methylglabridin, hispaglabridin A, stigmast-5-en-3-ol, stigmasta-5,3-dien-7-one, glabrol. Punica granatum extract contains hydroxymethylfurfural, stigmast-5-en-3-ol, 4h-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-, 1,2,3-benzenetriol, d-glucopyranose, 1,6-anhydro- as the major compounds. Among one hundred thirty screened compounds, twenty-one followed Lipinski’s rule of five and were nontoxic in nature. Docking results reveal that among all, β-sitosterol, stigmatsa-5,3-dien- 7-one, glabrol and 22,23-dibromostigmast-5-en-3-yl acetate (DBSA) showed the highest binding affinity with SMG1 i.e. -6.29 kcal/mol, -6.50 kcal/mol, -10.12 kcal/mol and -11.04 kcal/mol respectively as compared to standard inhibitor RHC 80267 (-5.83 kcal/mol). From the results, we conclude that the lead compounds may be used as potential anti-dandruff agents. Plant-based anti-dandruff products are eco-friendly and considered a safe alternative due to their less or negligible side effects.

Dissecting industrial fermentations of fine flavour cocoa through metagenomic analysis

The global demand for fine-flavour cocoa has increased worldwide during the last years. Fine-flavour cocoa offers exceptional quality and unique fruity and floral flavour attributes of high demand by the world's elite chocolatiers. Several studies have highlighted the relevance of cocoa fermentation to produce such attributes. Nevertheless, little is known regarding the microbial interactions and biochemistry that lead to the production of these attributes on farms of industrial relevance, where traditional fermentation methods have been pre-standardized and scaled up. In this study, we have used metagenomic approaches to dissect on-farm industrial fermentations of fine-flavour cocoa. Our results revealed the presence of a shared core of nine dominant microorganisms (i.e. Limosilactobacillus fermentum, Saccharomyces cerevisiae, Pestalotiopsis rhododendri, Acetobacter aceti group, Bacillus subtilis group, Weissella ghanensis group, Lactobacillus_uc, Malassezia restricta and Malassezia globosa) between two farms located at completely different agro-ecological zones. Moreover, a community metabolic model was reconstructed and proposed as a tool to further elucidate the interactions among microorganisms and flavour biochemistry. Our work is the first to reveal a core of microorganisms shared among industrial farms, which is an essential step to process engineering aimed to design starter cultures, reducing fermentation times, and controlling the expression of undesirable phenotypes.

Longitudinal study of the scalp microbiome suggests coconut oil to enrich healthy scalp commensals

Dandruff is a recurrent chronic scalp disorder, affecting majority of the population worldwide. Recently a metagenomic study of the Indian scalp microbiome described an imperative role of bacterial commensals in providing essential vitamins and amino acids to the scalp. Coconut oil and its formulations are commonly applied on the scalp in several parts of the world to maintain scalp health. Thus, in this study we examined the effect of topical application of coconut oil on the scalp microbiome (bacterial and fungal) at the taxonomic and functional levels and their correlation with scalp physiological parameters. A 16-weeks-long time-course study was performed including 12-weeks of treatment and 4-weeks of relapse phase on a cohort of 140 (70 healthy and 70 dandruff) Indian women, resulting in ~ 900 metagenomic samples. After the treatment phase, an increase in the abundance of Cutibacterium acnes and Malassezia globosa in dandruff scalp was observed, which were negatively correlated to dandruff parameters. At the functional level, an enrichment of healthy scalp-related bacterial pathways, such as biotin metabolism and decrease in the fungal pathogenesis pathways was observed. The study provides novel insights on the effect of coconut oil in maintaining a healthy scalp and in modulating the scalp microbiome.

Identification of Malassezia species using direct PCR-sequencing on clinical samples from patients with pityriasis versicolor and seborrheic dermatitis

Background and Purpose: Malassezia yeasts are lipophilic normal flora of the skin in humans and other warm-blooded vertebrates. This genus includes 18 species and is responsible for dermatological disorders, such as pityriasis versicolor, atopic dermatitis, seborrheic dermatitis, folliculitis, and dandruff. The aim of the present study was to identify the etiologic agents of Malassezia infections among the patients referring to the Referral Dermatology Clinic of Al-Zahra Hospital, Isfahan, Iran, during 2018-2019. Materials and Methods: For the purpose of the study, clinical specimens, including skin scrapings and dandruff, were collected and subjected to direct microscopy, culture, and polymerase chain reaction (PCR) sequencing. Direct PCR was performed on the clinical samples to amplify the D1/D2 region of 26S rDNA, using specific primers; subsequently, the amplicons were sent for sequencing. Results: This study was conducted on 120 patients with suspected pityriasis versicolor and seborrheic dermatitis, who referred to the Referral Dermatology Clinic of Al-Zahra Hospital, Isfahan, Iran, during 2018-2019. Out of this population, 50 (41.7%), 26 (52%), and 24 (48%) cases had Malassezia infection, pityriasis versicolor, and seborrheic dermatitis, respectively. Malassezia globosa was found to be the most prevalent species (n=29, 58%), followed by M. restricta (n=20, 40%), and M. arunalokei (n=1, 2%). Conclusion: The epidemiologic study was indicative of the frequency of some Malassezia species, such as M. globosa and M. restricta, in Isfahan, Iran. It can be concluded that direct PCR on clinical samples could be used as a simple, precise, effective, fast, and affordable method for research and even routine medical mycology laboratory studies.