A Stress Hub in Scedosporium apiospermum: The High Osmolarity Glycerol (HOG) Pathway

Yaakoub, Hajar; Mina, Sara; Marot, Agnès; Papon, Nicolas; Calenda, Alphonse; Bouchara, Jean-Philippe

doi:10.3390/kinasesphosphatases1010002

Cited by 2 publications

(2 citation statements)

References 32 publications

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“…The hyperactivation by both Scedosporium of glycolysis and glycerol metabolism at the early stages of voriconazole exposure also recalls what was observed in an azole-resistant Candida glabrata strain (Rogers et al 2006 ). Since voriconazole has been shown to induce a moderate activation of the High Osmolarity Glycerol (HOG) pathway in S. apiospermum (Yaakoub et al 2023 ), we also looked at the expression of the response regulator Ssk1 (g1351 and g9875 in S. aurantiacum MUT6114 and S. minutisporum MUT6113, respectively) and the key Mitogen-Activated Protein Kinase (MAPK) HOG1 (g7871 and g1735 in S. aurantiacum MUT6114 and S. minutisporum MUT6113, respectively) governing the pathway. The expression of Ssk1 did not show any significant change at any time point in both strains.…”

Section: Resultsmentioning

confidence: 99%

“…By contrast, HOG1 was down-regulated in S. aurantiacum MUT6114 at both time points, while S. minutisporum MUT6113 overexpressed the gene at 4 DPI. These contrasting results might be due to the fact that the HOG response in S. apiospermum is activated as early as one hour after the voriconazole treatment (Yaakoub et al 2023 ). In addition, the activation of HOG1 relies mainly on protein phosphorylation, rather than changes in its expression, and transcriptomics might not be the best tool to observe HOG pathway changes at these time points.…”

Section: Resultsmentioning

confidence: 99%

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The genomes of Scedosporium between environmental challenges and opportunism

Venice,

Spina,

Davolos

et al. 2023

IMA Fungus

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Emerging fungal pathogens are a global challenge for humankind. Many efforts have been made to understand the mechanisms underlying pathogenicity in bacteria, and OMICs techniques are largely responsible for those advancements. By contrast, our limited understanding of opportunism and antifungal resistance is preventing us from identifying, limiting and interpreting the emergence of fungal pathogens. The genus Scedosporium (Microascaceae) includes fungi with high tolerance to environmental pollution, whilst some species can be considered major human pathogens, such as Scedosporium apiospermum and Scedosporium boydii. However, unlike other fungal pathogens, little is known about the genome evolution of these organisms. We sequenced two novel genomes of Scedosporium aurantiacum and Scedosporium minutisporum isolated from extreme, strongly anthropized environments. We compared all the available Scedosporium and Microascaceae genomes, that we systematically annotated and characterized ex novo in most cases. The genomes in this family were integrated in a Phylum-level comparison to infer the presence of putative, shared genomic traits in filamentous ascomycetes with pathogenic potential. The analysis included the genomes of 100 environmental and clinical fungi, revealing poor evolutionary convergence of putative pathogenicity traits. By contrast, several features in Microascaceae and Scedosporium were detected that might have a dual role in responding to environmental challenges and allowing colonization of the human body, including chitin, melanin and other cell wall related genes, proteases, glutaredoxins and magnesium transporters. We found these gene families to be impacted by expansions, orthologous transposon insertions, and point mutations. With RNA-seq, we demonstrated that most of these anciently impacted genomic features responded to the stress imposed by an antifungal compound (voriconazole) in the two environmental strains S. aurantiacum MUT6114 and S. minutisporum MUT6113. Therefore, the present genomics and transcriptomics investigation stands on the edge between stress resistance and pathogenic potential, to elucidate whether fungi were pre-adapted to infect humans. We highlight the strengths and limitations of genomics applied to opportunistic human pathogens, the multifactoriality of pathogenicity and resistance to drugs, and suggest a scenario where pressures other than anthropic contributed to forge filamentous human pathogens.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The genomes of Scedosporium between environmental challenges and opportunism

Venice,

Spina,

Davolos

et al. 2023

IMA Fungus

View full text Add to dashboard Cite

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Polypeptides Targeting Paracoccidioides brasiliensis Drk1

Marcos,

de Oliveira,

Assato

et al. 2023

JoF

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Considering the toxicity of conventional therapeutic approaches and the importance of precise mechanistic targets, it is important to explore signaling pathways implicated in fungal pathobiology. Moreover, treatment of paracoccidioidomycosis, a systemic mycosis caused by a dimorphic fungus, requires prolonged therapeutic regimens. Among the numerous factors underpinning the establishment of Paracoccidioides spp. infection, the capacity to transition from the mycelial to the yeast form is of pivotal importance. The Drk1 protein of Paracoccidioides brasiliensis likely plays a decisive role in this morphological shift and subsequent virulence. We identified peptides with affinity for the PbDrk1 protein using the phage-display method and assessed the effects of these peptides on P. brasiliensis. The peptides were found to inhibit the phase transition of P. brasiliensis. Furthermore, a substantial proportion of these peptides prevented adhesion to pneumocytes. Although these peptides may not possess inherent antifungal properties, they can augment the effects of certain antifungal agents. Notably, the cell wall architecture of P. brasiliensis appears to be modulated by peptide intervention, resulting in a reduced abundance of glycosylated proteins and lipids. These peptides were also evaluated for their efficacy in a Galleria mellonella model and shown to contribute to enhanced larval survival rates. The role of PbDrk1, which is notably absent in mammals, should be further investigated to improve the understanding of its functional role in P. brasiliensis, which may be helpful for designing novel therapeutic modalities.

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A Stress Hub in Scedosporium apiospermum: The High Osmolarity Glycerol (HOG) Pathway

Cited by 2 publications

References 32 publications

The genomes of Scedosporium between environmental challenges and opportunism

The genomes of Scedosporium between environmental challenges and opportunism

Polypeptides Targeting Paracoccidioides brasiliensis Drk1

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