Dataset Information

Global Analysis of Cell Wall Genes Revealed Putative Virulence Factors in the Dermatophyte Trichophyton rubrum.

ABSTRACT: The fungal cell wall is a structure in constant contact with the external environment. It confers shape to the cell and protects it from external threats. During host adaptation, the cell wall structure of fungal pathogens is continuously reshaped by the orchestrated action of numerous genes. These genes respond to environmental stresses and challenging growth conditions, influencing the infective potential of the fungus. Here, we aimed to identify cell wall biosynthesis-related genes that putatively encode virulence factors in Trichophyton rubrum. We used RNA-seq to examine the impact of two drugs, namely undecanoic acid, and acriflavine as well as the effects of the carbon source switching from glucose to keratin on T. rubrum cell wall metabolism. By using functional annotation based on Gene Ontology terms, we identified significantly differentially expressed cell wall-related genes in all stress conditions. We also exposed T. rubrum to osmotic and other cell wall stressors and evaluated the susceptibility and gene modulation in response to stress. The changes in the ambient environment caused continuous cell wall remodeling, forcing the fungus to undergo modulatory restructuring. The influence of the external challenges indicated a highly complex response pattern. The genes that were modulated simultaneously in the three stress conditions highlight potential targets for antifungal development.

SUBMITTER: Martins MP

PROVIDER: S-EPMC6761320 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Global Analysis of Cell Wall Genes Revealed Putative Virulence Factors in the Dermatophyte <i>Trichophyton rubrum</i>.

Martins Maíra P MP Silva Larissa G LG Rossi Antonio A Sanches Pablo R PR Souza Larissa D R LDR Martinez-Rossi Nilce M NM

Frontiers in microbiology 20190919

The fungal cell wall is a structure in constant contact with the external environment. It confers shape to the cell and protects it from external threats. During host adaptation, the cell wall structure of fungal pathogens is continuously reshaped by the orchestrated action of numerous genes. These genes respond to environmental stresses and challenging growth conditions, influencing the infective potential of the fungus. Here, we aimed to identify cell wall biosynthesis-related genes that putat ...[more]

PMID: 31608026

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Project description:Purpose: We evaluated T. rubrum transcriptome using high-throughput RNA-sequencing (RNA-seq) technology aiming to identify metabolic pathways modulated the development in keratin. Methods: T. rubrum strain CBS118892 was inoculated into 100 mL Sabouraud dextrose broth, and incubated under agitation at 28 °C for 96 h. Mycelia were aseptically transferred into 100 mL minimal medium (MM) at pH 5.0 containing 70 mM nitrate and 50 mM glucose (control) or 0.5% (w/v) bovine keratin (treatment) as the carbon source. The cultures were incubated under agitation at 28 °C for 24 h, 48 h, or 96 h. Equal amounts of RNA from three independent biological replicates of keratin or glucose cultures were sequenced with a Hiseq 2000 sequencer. Paired-end reads 150 bp in size were generated. Raw read data obtained were filtered for quality control by FastQC tool and trimmed with Trimmomatic to remove adapters and Illumina-specific sequences. Trimmed paired-end reads from each sample were aligned to the T. rubrum reference genome. Gene-level read counts were quantified with STAR’s ‘-quantModeGeneCounts’ parameter. Differential expression was analyzed with the DESeq2 bioconductor package. A Benjamini-Hochberg correction adjusted the P threshold and was applied to reveal statistically significant changes in gene expression levels. It was set to 0.05, with a log2 fold change ± 1.5 and postulated as a significantly modulated transcript abundance level. Genes surpassing these thresholds are hereinafter referred to as differentially expressed genes (DEG). They were functionally categorized with the Gene Ontology (GO) terms assigned by the Blast2GO algorithm. Highly represented categories were determined by enrichment analysis with the BayGO algorithm. Results: Our results present adaptive strategies in response to culture media. The global modulation in response to keratin supports fungal virulence and proper adaptation to the environment, in comparison to the availability of glucose as a carbon source. Conclusions: Our results revealed a profile of the adaptive events to the host environment, crucial to the establishment and maintenance of the infection. The observed metabolic modulation is necessary for fungus survival and perpetuation in the initial steps of the infective process in their host.

Project description:Fungal infections represent a significant concern worldwide, contributing to human morbidity and mortality. Dermatophyte infections are among the most significant mycoses, and Trichophyton rubrum appears to be the principal causative agent. Thus, an understanding of its pathophysiology is urgently required. Several lines of evidence have demonstrated that the APSES family of transcription factors (Asm1p, Phd1p, Sok2p, Efg1p, and StuA) is an important point of vulnerability in fungal pathogens and a potential therapeutic target. These transcription factors are unique to fungi, contributing to cell differentiation and adaptation to environmental cues and virulence. It has recently been demonstrated that StuA plays a pleiotropic role in dermatophyte pathophysiology. It was suggested that it functions as a mediator of crosstalk between different pathways that ultimately contribute to adaptive responses and fungal-host interactions. The complex regulation of StuA and its interaction pathways are yet to be unveiled. Thus, this study aimed to gain a deeper understanding of StuA-regulated processes in T. rubrum by assessing global gene expression following growth on keratin or glucose sources. The data showed the involvement of StuA in biological processes related to central carbon metabolism and glycerol catabolism, reactive oxygen species metabolism, and cell wall construction. Changes in carbohydrate metabolism may be responsible for the significant alteration in cell wall pattern and consequently in cell-cell interaction and adhesion. Loss of StuA led to impaired biofilm production and promoted proinflammatory cytokine secretion in a human keratinocyte cell line. We also observed the StuA-dependent regulation of catalase genes. Altogether, these data demonstrate the multitude of regulatory targets of StuA with a critical role in central metabolism that may ultimately trigger a cascade of secondary effects with substantial impact on fungal physiology and virulence traits.

Dataset Information

Global Analysis of Cell Wall Genes Revealed Putative Virulence Factors in the Dermatophyte Trichophyton rubrum.

Publications

Global Analysis of Cell Wall Genes Revealed Putative Virulence Factors in the Dermatophyte <i>Trichophyton rubrum</i>.

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