The CCAAT‐binding complex mediates azole susceptibility of <i>Aspergillus fumigatus</i> by suppressing SrbA expression and cleavage

Zhang, Chi; Gao, Lu; Ren, Yi-Ran; Gu, Huiyu; Zhang, Yuanwei; Lü, Ling

doi:10.1002/mbo3.1249

Cited by 5 publications

(2 citation statements)

References 68 publications

(105 reference statements)

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“…Then, 100% trichloroacetic acid was added to precipitate the protein after thorough vortexing. After centrifugation at 4°C, the precipitate was collected and then heated at 95°C for 5 min ( 56 , 57 ). Western blotting was then performed to detect the phosphorylation level of MpkA using anti-phospho-ERK1-T202/Y204+ERK2-T185/Y187 (1:2,000, ABclonal Technology Co.) as the primary antibody and anti-rabbit (1:5,000, ABclonal Technology Co.) as the secondary antibody.…”

Section: Methodsmentioning

confidence: 99%

The EH domain-containing protein, EdeA, is involved in endocytosis, cell wall integrity, and pathogenicity in Aspergillus fumigatus

Dai,

Liu,

Goldman

et al. 2024

mSphere

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Endocytosis has been extensively studied in yeasts, where it plays crucial roles in growth, signaling regulation, and cell-surface receptor internalization. However, the biological functions of endocytosis in pathogenic filamentous fungi remain largely unexplored. In this study, we aimed to functionally characterize the roles of EdeA, an ortholog of the Saccharomyces cerevisiae endocytic protein Ede1, in Aspergillus fumigatus . EdeA was observed to be distributed as patches on the plasma membrane and concentrated in the subapical collar of hyphae, a localization characteristic of endocytic proteins. Loss of edeA caused defective hyphal polarity, reduced conidial production, and fewer sites of endocytosis initiations than that of the parental wild type. Notably, the edeA null mutant exhibited increased sensitivity to cell wall-disrupting agents, indicating a role for EdeA in maintaining cell wall integrity in A. fumigatus . This observation was further supported by the evidence showing that the thickness of the cell wall in the Δ edeA mutant increased, accompanied by abnormal activation of MpkA, a key component in the cell wall integrity pathway. Additionally, the Δ edeA mutant displayed increased pathogenicity in the Galleria mellonella wax moth infection model, possibly due to alterations in cell wall morphology. Site-directed mutagenesis identified the conserved residue E348 within the third EH ( E ps15 h omology) domain of EdeA as crucial for its subcellular localization and functions. In conclusion, our results highlight the involvement of EdeA in endocytosis, hyphal polarity, cell wall integrity, and pathogenicity in A. fumigatus . IMPORTANCE Aspergillus fumigatus is a significant human pathogenic fungus known to cause invasive aspergillosis, a disease with a high mortality rate. Understanding the basic principles of A. fumigatus pathogenicity is crucial for developing effective strategies against this pathogen. Previous research has underscored the importance of endocytosis in the infection capacity of pathogenic yeasts; however, its biological function in pathogenic mold remains largely unexplored. Our characterization of EdeA in A. fumigatus sheds light on the role of endocytosis in the development, stress response, and pathogenicity of pathogenic molds. These findings suggest that the components of the endocytosis process may serve as potential targets for antifungal therapy.

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Section: Methodsmentioning

confidence: 99%

The EH domain-containing protein, EdeA, is involved in endocytosis, cell wall integrity, and pathogenicity in Aspergillus fumigatus

Dai,

Liu,

Goldman

et al. 2024

mSphere

Self Cite

View full text Add to dashboard Cite

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“…In a mouse model, the mitochondrial respiration chain component cycA (cytochrome C gene) and alcC (alcohol dehydrogenase gene) deleted strains have been come out the defect virulence (Grahl et al 2012(Grahl et al , 2011. Chromatin immunoprecipitation followed by parallel DNA sequencing showed that SrbA (sterol regulatory element-binding protein gene) helped regulate ergosterol biosynthesis and iron uptake during hypoxic conditions or iron limitation (Zhang et al 2021a). Critically, the lung is a "sponge," and there are not enough carbon or nitrogen sources on lung surfaces to limit A. fumigatus growth.…”

Section: A Fumigatus Survival Strategies In Hostsmentioning

confidence: 99%

Aspergillus fumigatus escape mechanisms from its harsh survival environments

Liu,

Zeng,

Zhou

et al. 2024

Appl Microbiol Biotechnol

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Aspergillus fumigatus is a ubiquitous pathogenic mold and causes several diseases, including mycotoxicosis, allergic reactions, and systemic diseases (invasive aspergillosis), with high mortality rates. In its ecological niche, the fungus has evolved and mastered many reply strategies to resist and survive against negative threats, including harsh environmental stress and deficiency of essential nutrients from natural environments, immunity responses and drug treatments in host, and competition from symbiotic microorganisms. Hence, treating A. fumigatus infection is a growing challenge. In this review, we summarized A. fumigatus reply strategies and escape mechanisms and clarified the main competitive or symbiotic relationships between A. fumigatus, viruses, bacteria, or fungi in host microecology. Additionally, we discussed the contemporary drug repertoire used to treat A. fumigatus and the latest evidence of potential resistance mechanisms. This review provides valuable knowledge which will stimulate further investigations and clinical applications for treating and preventing A. fumigatus infections. Key points • Harsh living environment was a great challenge for A. fumigatus survival. • A. fumigatus has evolved multiple strategies to escape host immune responses. • A. fumigatus withstands antifungal drugs via intrinsic escape mechanisms.

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An investigation into the transcription factors and regulatory mechanisms of Aspergillus

Qin,

Yu,

Tian

2024

Food Safety and Health

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Aflatoxins produced by Aspergillus flavus, a group of filamentous fungi widely distributed in nature as foodborne pathogens, are a major threat to food safety. It is thus clear that Aspergillus is inextricably linked to the food sector. Transcription factors enable the correct expression of genes at specific spatial and temporal levels, and they constitute a considerable proportion of the fungal genome sequence. Their presence is particularly important for growth, secondary metabolism, stress response, and pathogenic process of Aspergillus. This article reviews the functional regulatory mechanisms of important transcription factors in the foodborne pathogen Aspergillus flavus and other Aspergillus species, the current status of research technologies, and the potential value of applying them to diverse fields such as food safety, biotechnology, medical health, and agricultural output in the future.

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The CCAAT‐binding complex mediates azole susceptibility of Aspergillus fumigatus by suppressing SrbA expression and cleavage

Cited by 5 publications

References 68 publications

The EH domain-containing protein, EdeA, is involved in endocytosis, cell wall integrity, and pathogenicity in Aspergillus fumigatus

The EH domain-containing protein, EdeA, is involved in endocytosis, cell wall integrity, and pathogenicity in Aspergillus fumigatus

Aspergillus fumigatus escape mechanisms from its harsh survival environments

An investigation into the transcription factors and regulatory mechanisms of Aspergillus

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