Expression of genes containing tandem repeat patterns involved in the fungal‐host interaction and in the response to antifungals in Trichophyton rubrum

Mycoses ◽  
2020 ◽  
Vol 63 (6) ◽  
pp. 610-616 ◽  
Author(s):  
Mariana Heinzen Abreu ◽  
Tamires Aparecida Bitencourt ◽  
Matheus Eloy Franco ◽  
Igor Sawasaki Moreli ◽  
Bruna Aline Michelotto Cantelli ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Trichophyton Rubrum ◽  
Fungal Host ◽  
Host Interaction ◽  
Expression Of Genes

scholarly journals Dual RNA-Seq Analysis of Trichophyton rubrum and HaCat Keratinocyte Co-Culture Highlights Important Genes for Fungal-Host Interaction

Genes ◽  
2018 ◽  
Vol 9 (7) ◽  
pp. 362 ◽  
Author(s):  
Monise Petrucelli ◽  
Kamila Peronni ◽  
Pablo Sanches ◽  
Tatiana Komoto ◽  
Josie Matsuda ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Trichophyton Rubrum ◽  
Glyoxylate Cycle ◽  
Human Keratinocytes ◽  
Rna Seq ◽  
Fungal Host ◽  
Host Interaction ◽  
Genes Encoding ◽  
Hacat Keratinocyte

The dermatophyte Trichophyton rubrum is the major fungal pathogen of skin, hair, and nails that uses keratinized substrates as the primary nutrients during infection. Few strategies are available that permit a better understanding of the molecular mechanisms involved in the interaction of T. rubrum with the host because of the limitations of models mimicking this interaction. Dual RNA-seq is a powerful tool to unravel this complex interaction since it enables simultaneous evaluation of the transcriptome of two organisms. Using this technology in an in vitro model of co-culture, this study evaluated the transcriptional profile of genes involved in fungus-host interactions in 24 h. Our data demonstrated the induction of glyoxylate cycle genes, ERG6 and TERG_00916, which encodes a carboxylic acid transporter that may improve the assimilation of nutrients and fungal survival in the host. Furthermore, genes encoding keratinolytic proteases were also induced. In human keratinocytes (HaCat) cells, the SLC11A1, RNASE7, and CSF2 genes were induced and the products of these genes are known to have antimicrobial activity. In addition, the FLG and KRT1 genes involved in the epithelial barrier integrity were inhibited. This analysis showed the modulation of important genes involved in T. rubrum–host interaction, which could represent potential antifungal targets for the treatment of dermatophytoses.

scholarly journals StuA-Regulated Processes in the Dermatophyte Trichophyton rubrum: Transcription Profile, Cell-Cell Adhesion, and Immunomodulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Tamires A. Bitencourt ◽  
João Neves-da-Rocha ◽  
Maira P. Martins ◽  
Pablo R. Sanches ◽  
Elza A. S. Lang ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factors ◽  
Fungal Pathogens ◽  
Trichophyton Rubrum ◽  
Fungal Infections ◽  
Critical Role ◽  
Cell Interaction ◽  
Substantial Impact ◽  
Fungal Host ◽  
Cell Cell

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.

scholarly journals Gene Expression Response ofTrichophyton rubrumduring Coculture on Keratinocytes Exposed to Antifungal Agents

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Tatiana Takahasi Komoto ◽  
Tamires Aparecida Bitencourt ◽  
Gabriel Silva ◽  
Rene Oliveira Beleboni ◽  
Mozart Marins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Citrate Synthase ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Serine Proteinase ◽  
Gene Expression Response ◽  
Fungal Host ◽  
Host Interaction ◽  
Genes Encoding

Trichophyton rubrumis the most common causative agent of dermatomycoses worldwide, causing infection in the stratum corneum, nails, and hair. Despite the high prevalence of these infections, little is known about the molecular mechanisms involved in the fungal-host interaction, particularly during antifungal treatment. The aim of this work was to evaluate the gene expression ofT. rubrumcocultured with keratinocytes and treated with the flavonoidtrans-chalcone and the glycoalkaloidα-solanine. Both substances showed a marked antifungal activity againstT. rubrumstrain CBS (MIC = 1.15 and 17.8 µg/mL, resp.). Cytotoxicity assay against HaCaT cells produced IC50values of 44.18 totrans-chalcone and 61.60 µM toα-solanine. The interaction of keratinocytes withT. rubrumconidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporterTruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, andTruMDR2 genes. Furthermore, thetrans-chalcone downregulated the genes involved in the glyoxylate pathway, isocitrate lyase, and citrate synthase. Considering the urgent need for more efficient and safer antifungals, these results contribute to a better understanding of fungal-host interactions and to the discovery of new antifungal targets.

scholarly journals Transcription profile of Trichophyton rubrum conidia grown on keratin reveals the induction of an adhesin-like protein gene with a tandem repeat pattern

BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Tamires Aparecida Bitencourt ◽  
Claudia Macedo ◽  
Matheus Eloy Franco ◽  
Amanda Freire Assis ◽  
Tatiana Takahasi Komoto ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Protein Gene ◽  
Trichophyton Rubrum ◽  
Transcription Profile ◽  
Repeat Pattern

scholarly journals Modulation of the Fungal-Host Interaction by the Intra-Species Diversity of C. albicans

Pathogens ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 11 ◽  
Author(s):  
◽  
Keyword(s):  
Fungal Pathogen ◽  
Fungal Species ◽  
Protective Mechanisms ◽  
Fungal Host ◽  
Host Interaction ◽  
Immunosuppressed Patients ◽  
Natural Diversity ◽  
Opportunistic Fungal Pathogen ◽  
Fungal Interactions ◽  
Human Infections

The incidence of human infections caused by the opportunistic fungal pathogen Candida albicans is on the rise due to increasing numbers of immunosuppressed patients. The importance of the immune system in preventing overgrowth of the colonizing fungus and thereby limiting infection is well recognized and host protective mechanisms widely investigated. Only recently, it was recognized that the natural diversity in the fungal species could also influence the outcome of the interaction between the fungus and the host. C. albicans strain-specific differences are complex and their regulation at the genomic, genetic, and epigenetic level and by environmental factors is only partially understood. In this review, we provide an overview of the natural diversity of C. albicans and discuss how it impacts host-fungal interactions and thereby affects the balance between commensalism versus disease.

scholarly journals Comparative Transcriptome Analysis of Two Cucumber Cultivars with Different Sensitivity to Cucumber Mosaic Virus Infection

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 145
Author(s):  
Zdeno Šubr ◽  
Lukáš Predajňa ◽  
Katarína Šoltys ◽  
Boris Bokor ◽  
Jaroslav Budiš ◽  
...  
Keyword(s):  
Cucumber Mosaic Virus ◽  
Mosaic Virus ◽  
New Technologies ◽  
Specific Gene ◽  
Broad Host Range ◽  
Sources Of Resistance ◽  
Host Interaction ◽  
Expression Of Genes ◽  
Computer Based ◽  
Different Response

Cucumber mosaic virus (CMV), with extremely broad host range including both monocots and dicots around the world, belongs to most important viral crop threats. Either natural or genetically constructed sources of resistance are being intensively investigated; for this purpose, exhaustive knowledge of molecular virus-host interaction during compatible and incompatible infection is required. New technologies and computer-based “omics” on various levels contribute markedly to this topic. In this work, two cucumber cultivars with different response to CMV challenge were tested, i.e., sensitive cv. Vanda and resistant cv. Heliana. The transcriptomes were prepared from both cultivars at 18 days after CMV or mock inoculation. Subsequently, four independent comparative analyses of obtained data were performed, viz. mock- and CMV-inoculated samples within each cultivar, samples from mock-inoculated cultivars to each other and samples from virus-inoculated cultivars to each other. A detailed picture of CMV-influenced genes, as well as constitutive differences in cultivar-specific gene expression was obtained. The compatible CMV infection of cv. Vanda caused downregulation of genes involved in photosynthesis, and induction of genes connected with protein production and modification, as well as components of signaling pathways. CMV challenge caused practically no change in the transcription profile of the cv. Heliana. The main differences between constitutive transcription activity of the two cultivars relied in the expression of genes responsible for methylation, phosphorylation, cell wall organization and carbohydrate metabolism (prevailing in cv. Heliana), or chromosome condensation and glucan biosynthesis (prevailing in cv. Vanda). Involvement of several genes in the resistant cucumber phenotype was predicted; this can be after biological confirmation potentially applied in breeding programs for virus-resistant crops.

scholarly journals Dynamics of SARS-CoV-2 host cell interactions inferred from transcriptome analyses

2021 ◽  
Author(s):  
Lukas Adam ◽  
Megan Stanifer ◽  
Fabian Springer ◽  
Jan Mathony ◽  
Chiara Di Ponzio ◽  
...  
Keyword(s):  
Host Cell ◽  
Virus Replication ◽  
Transcriptional Activation ◽  
Transcriptional Response ◽  
Cytochrome P450 Enzymes ◽  
Time Resolved ◽  
Viral Response ◽  
Host Interaction ◽  
Iterative Model ◽  
Expression Of Genes

The worldwide spread of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) caused an urgent need for an in-depth understanding of interactions between the virus and its host. Here, we dissected the dynamics of virus replication and the host cell transcriptional response to SARS-CoV-2 infection at a systems level by combining time-resolved RNA sequencing with mathematical modeling. We observed an immediate transcriptional activation of inflammatory pathways linked to the anti-viral response followed by increased expression of genes involved in ribosome and mitochondria function, thus hinting at rapid alterations in protein production and cellular energy supply. At later stages, metabolic processes, in particular those depending on cytochrome P450 enzymes, were downregulated. To gain a deeper understanding of the underlying transcriptional dynamics, we developed an ODE model of SARS-CoV-2 infection and replication. Iterative model reduction and refinement revealed that a negative feedback from virus proteins on the expression of anti-viral response genes was essential to explain our experimental dataset. Our study provides insights into SARS-CoV-2 virus-host interaction dynamics and facilitates the identification of druggable host pathways supporting virus replication.

scholarly journals The Transcriptional Profile of Trichophyton rubrum Co-Cultured with Human Keratinocytes Shows New Insights about Gene Modulation by Terbinafine

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 274 ◽  
Author(s):  
Monise Fazolin Petrucelli ◽  
Josie Budag Matsuda ◽  
Kamila Peroni ◽  
Pablo Rodrigo Sanches ◽  
Wilson Araújo Silva ◽  
...  
Keyword(s):  
Trichophyton Rubrum ◽  
Human Keratinocytes ◽  
Major Facilitator Superfamily ◽  
Ergosterol Biosynthesis ◽  
Rna Seq ◽  
Host Interaction ◽  
Culture Model ◽  
Superficial Mycosis ◽  
Genes Encoding ◽  
Major Facilitator

The dermatophyte Trichophyton rubrum is the main causative agent of dermatophytoses worldwide. Although a superficial mycosis, its incidence has been increasing especially among diabetic and immunocompromised patients. Terbinafine is commonly used for the treatment of infections caused by dermatophytes. However, cases of resistance of T. rubrum to this allylamine were reported even with the efficacy of this drug. The present study is the first to evaluate the effect of terbinafine using a co-culture model of T. rubrum and human keratinocytes, mimicking a fungus-host interaction, in conjunction with RNA-seq technique. Our data showed the repression of several genes involved in the ergosterol biosynthesis cascade and the induction of genes encoding major facilitator superfamily (MFS)- and ATP-binding cassette superfamily (ABC)-type membrane transporter which may be involved in T. rubrum mechanisms of resistance to this drug. We observed that some genes reported in the scientific literature as candidates of new antifungal targets were also modulated. In addition, we found the modulation of several genes that are hypothetical in T. rubrum but that possess known orthologs in other dermatophytes. Taken together, the results indicate that terbinafine can act on various targets related to the physiology of T. rubrum other than its main target of ergosterol biosynthetic pathway.

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