Dataset Information

Whole-Genome Analysis Illustrates Global Clonal Population Structure of the Ubiquitous Dermatophyte Pathogen Trichophyton rubrum.

ABSTRACT: Dermatophytes include fungal species that infect humans, as well as those that also infect other animals or only grow in the environment. The dermatophyte species Trichophyton rubrum is a frequent cause of skin infection in immunocompetent individuals. While members of the T. rubrum species complex have been further categorized based on various morphologies, their population structure and ability to undergo sexual reproduction are not well understood. In this study, we analyze a large set of T. rubrum and T. interdigitale isolates to examine mating types, evidence of mating, and genetic variation. We find that nearly all isolates of T. rubrum are of a single mating type, and that incubation with T. rubrum "morphotype" megninii isolates of the other mating type failed to induce sexual development. While the region around the mating type locus is characterized by a higher frequency of SNPs compared to other genomic regions, we find that the population is remarkably clonal, with highly conserved gene content, low levels of variation, and little evidence of recombination. These results support a model of recent transition to asexual growth when this species specialized to growth on human hosts.

SUBMITTER: Persinoti GF

PROVIDER: S-EPMC5887155 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Whole-Genome Analysis Illustrates Global Clonal Population Structure of the Ubiquitous Dermatophyte Pathogen Trichophyton rubrum.

Persinoti Gabriela F GF Martinez Diego A DA Li Wenjun W Döğen Aylin A Billmyre R Blake RB Averette Anna A Goldberg Jonathan M JM Shea Terrance T Young Sarah S Zeng Qiandong Q Oliver Brian G BG Barton Richard R Metin Banu B Hilmioğlu-Polat Süleyha S Ilkit Macit M Gräser Yvonne Y Martinez-Rossi Nilce M NM White Theodore C TC Heitman Joseph J Cuomo Christina A CA

Genetics 20180221 4

Dermatophytes include fungal species that infect humans, as well as those that also infect other animals or only grow in the environment. The dermatophyte species Trichophyton rubrum is a frequent cause of skin infection in immunocompetent individuals. While members of the T. rubrum species complex have been further categorized based on various morphologies, their population structure and ability to undergo sexual reproduction are not well understood. In this study, we analyze a la ...[more]

PMID: 29467168

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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

Whole-Genome Analysis Illustrates Global Clonal Population Structure of the Ubiquitous Dermatophyte Pathogen Trichophyton rubrum.

Publications

Whole-Genome Analysis Illustrates Global Clonal Population Structure of the Ubiquitous Dermatophyte Pathogen <i>Trichophyton rubrum</i>.

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