Dataset Information

The Transcription Factor StuA Regulates the Glyoxylate Cycle in the Dermatophyte Trichophyton rubrum under Carbon Starvation.

ABSTRACT: Trichophyton rubrum is the primary causative agent of dermatophytosis worldwide. This fungus colonizes keratinized tissues and uses keratin as a nutritional source during infection. In T. rubrum-host interactions, sensing a hostile environment triggers the adaptation of its metabolic machinery to ensure its survival. The glyoxylate cycle has emerged as an alternative metabolic pathway when glucose availability is limited; this enables the conversion of simple carbon compounds into glucose via gluconeogenesis. In this study, we investigated the impact of stuA deletion on the response of glyoxylate cycle enzymes during fungal growth under varying culture conditions in conjunction with post-transcriptional regulation through alternative splicing of the genes encoding these enzymes. We revealed that the ΔstuA mutant downregulated the malate synthase and isocitrate lyase genes in a keratin-containing medium or when co-cultured with human keratinocytes. Alternative splicing of an isocitrate lyase gene yielded a new isoform. Enzymatic activity assays showed specific instances where isocitrate lyase and malate synthase activities were affected in the mutant strain compared to the wild type strain. Taken together, our results indicate a relevant balance in transcriptional regulation that has distinct effects on the enzymatic activities of malate synthase and isocitrate lyase.

SUBMITTER: Petrucelli MF

PROVIDER: S-EPMC10778625 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Transcription Factor StuA Regulates the Glyoxylate Cycle in the Dermatophyte Trichophyton rubrum under Carbon Starvation.

Petrucelli Monise Fazolin MF Martins-Santana Leonardo L Sanches Pablo R PR Oliveira Vanderci M VM Rossi Antonio A Martinez-Rossi Nilce M NM

International journal of molecular sciences 20231228 1

Trichophyton rubrum is the primary causative agent of dermatophytosis worldwide. This fungus colonizes keratinized tissues and uses keratin as a nutritional source during infection. In T. rubrum-host interactions, sensing a hostile environment triggers the adaptation of its metabolic machinery to ensure its survival. The glyoxylate cycle has emerged as an alternative metabolic pathway when glucose availability is limited; this enables the conversion of simple carbon compounds into ...[more]

PMID: 38203573

Similar Datasets

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.

Project description:Purpose: We aimed to gain more aspects about Stua-regulated processes in T. rubrum by assessing the global gene expression after its growth on keratin or glucose sources. Methods: T. rubrum strain CBS118892 and the null mutant strain ΔstuA were 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 (test condition) as an alternative 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 NextSeq 500 sequencer. Paired-end reads of 150 bp in size were generated. Raw data obtained were processed 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, and a cut off threshold of ±1.5 log2-fold change was set to reveal statistically significant changes in expression levels, and referred as differentially expressed genes (DEG). DEGs were functionally categorized with the Gene Ontology (GO) terms assigned by the Blast2GO algorithm. Ultimately, the most representative categories for each experimental condition were identified by enrichment analysis using the BayGO algorithm . Results: Our data showed the involvement of Stua in biological processes related to carbon central metabolism and glycerol catabolism, ROS metabolism, and cell wall construction. The deep changes in carbohydrate metabolism might be responsible for significant alteration in cell wall pattern and consequently in cell to cell interaction and adhesion as we also demonstrated in this study. The mutant strain presented an impairment in biofilm production and promoted an increase in pro-inflammatory cytokine secretion. Moreover, we displayed a StuA-dependent regulation on catalase genes. Conclusions: In conclusion, our data demonstrated the multitude of regulatory targets in TrStuA with a critical role in central metabolism that ultimately may be responsible to trigger a cascade of secondary effects with strong impacts on fungal physiology and virulence traits.

Dataset Information

The Transcription Factor StuA Regulates the Glyoxylate Cycle in the Dermatophyte Trichophyton rubrum under Carbon Starvation.

Publications

The Transcription Factor StuA Regulates the Glyoxylate Cycle in the Dermatophyte <i>Trichophyton rubrum</i> under Carbon Starvation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets