Abstract
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.
Highlights
The interaction between fungi and their hosts involves a plethora of molecular pathways that synergize to sense and respond to changes in the surrounding milieu (Burmester et al, 2011; Peres et al, 2016; Martinez-Rossi et al, 2017)
A total of 1,170 Differentially expressed genes (DEGs) were identified in samples grown in glucose and 1,230 DEGs in samples grown with keratin
Under the lens of high-throughput approaches, it is possible to uncover some of the mechanisms governed by transcription factors
Summary
The interaction between fungi and their hosts involves a plethora of molecular pathways that synergize to sense and respond to changes in the surrounding milieu (Burmester et al, 2011; Peres et al, 2016; Martinez-Rossi et al, 2017). Signal transduction plays an important role to enable cell responsiveness in a stimulus-specific manner. Fungal cells have the refined ability to discriminate environmental signals and tune their metabolism to deal with changing conditions. Transduction pathways are highly conserved between divergent fungal species due to their adaptive value from an evolutionary perspective (Lengeler et al, 2000). Extracellular molecules can trigger alterations in the host immune response, impacting on the fungus metabolism and promoting cell structural modifications, thereby altering the infection outcome (Munoz et al, 2019). Invasion success strictly depends on a balance between virulence, responsiveness, and the ability to inhibit the host defense mechanisms
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