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Comparative Analysis of Antifungal Mechanism of Lauryl betaine in the Human Fungal Pathogens Cryptococcus neoformans and Malassezia restricta

ABSTRACT: Purpose: Understanding the mechanism of action of lauryl betaine against Cryptococcus neoformans and Malassezia restricta. Methods: The transcriptome profile of the lauryl betaine-treated cells compared to that of untreated cells were generated by RNA-seq Illumina Hiseq. Results: A number of genes were differentially expressed in the lauryl betaine-treated cells, which include genes involved in ergosterol biosynthetic pathway.

ORGANISM(S): Malassezia restricta Cryptococcus neoformans H99

PROVIDER: GSE124734 | GEO | 2019/08/22

REPOSITORIES: GEO

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Comparative Analysis of Antifungal Mechanism of Lauryl betaine in the Human Fungal Pathogens Cryptococcus neoformans and Malassezia restricta

Project description:Comparative Analysis of Antifungal Mechanism of Lauryl betaine in the Human Fungal Pathogens Cryptococcus neoformans and Malassezia restricta

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Project description:Purpose: Understanding the Mechanism of Action of the Anti-Dandruff Agent Zinc Pyrithione against Malassezia restricta. Methods: The transcriptome profile of the ZPT-treated M. restricta cells compared to that of untreated cells were generated by RNA-Seq using Illumina HiSeq. Generated raw reads that passed quality filters were mapped to the reference genome. Mapped reads were counted by featureCounts in Subread package v1.4.3 and the relative transcript abundance was TPM-normalized. Results: A number of genes were differentially expressed in the ZPT-treated cells, which include genes involved in zinc transporter, mitochondirial function, TCA cycle, electron transport chain and lipase.

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Acetic acid produced by Staphylococcus epidermidis remodels chromatin architecture and suppresses gene expression in Malassezia restricta [Hi-C]

Project description:Malassezia restricta and Staphylococcus epidermidis are dominant members of the human skin microbiome that interact closely, yet the molecular basis of their interaction remains unclear. In this study, we investigated how S. epidermidis-derived acetic acid (AcOH) influences chromatin organization in M. restricta. We generated the first high-resolution three-dimensional genome architecture map of M. restricta using in situ Hi-C and identified putative centromeric regions based on inter-chromosomal contact patterns. Exposure to AcOH, either by co-culture or direct treatment, led to large-scale chromatin decompaction and enhanced centromere clustering. These findings indicate that AcOH acts as an epigenetic modulator, inducing significant reorganization of nuclear architecture in M. restricta. This dataset provides a resource for understanding interkingdom interactions and the epigenetic effects of bacterial metabolites on fungal chromatin structure.

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Antifungal Mechanism of Action of Lauryl Betaine Against Skin-Associated Fungus <i>Malassezia restricta</i>.

Project description:Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.

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Project description:To understand ketoconazole resistance mechanism in M. restricta, we investigated differentially expressed genes in the azole resistant isolates using transcriptome profile. Transcriptomes of ketoconazole susceptible and resistant M. restricta cells in the absence and precence of ketoconazole were compared and analyzed by RNA sequencing.

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