The structural unit of melanin in the cell wall of the fungal pathogen Cryptococcus neoformans

Camacho, Emma; Vij, Raghav; Chrissian, Christine; Prados-Rosales, Rafael; Gil, David; O’Meally, Robert N.; Cordero, Radamés J. B.; Cole, Robert N.; McCaffery, J. Michael; Stark, Ruth E.; Casadevall, Arturo

doi:10.1074/jbc.ra119.008684

Cited by 91 publications

(117 citation statements)

References 95 publications

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“…Melanin is not only bound to the cell wall, but can also be transported out of the cell embedded in EVs as melanin granules, as has been shown for the opportunistic pathogenic fungus Cryptococcus neoformans [95]. The attachment of melanin to the cryptococcal cell wall and the detection of 200 nm spherical structures were also reported by Camacho et al [96]. The other melanin study by Upadhyay et al [97] showed the trafficking of melanin enzymes to endosomes or multivesicular bodies (MVBs), which are a possible biosynthetic machinery of EVs.…”

Section: Discussionsupporting

confidence: 53%

The Neurotropic Black Yeast Exophiala dermatitidis Induces Neurocytotoxicity in Neuroblastoma Cells and Progressive Cell Death

Lavrin

Konte

Kostanjšek

et al. 2020

Cells

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The neurotropic and extremophilic black yeast Exophiala dermatitidis (Herpotrichellaceae) inhabits diverse indoor environments, in particular bathrooms, steam baths, and dishwashers. Here, we show that the selected strain, EXF-10123, is polymorphic, can grow at 37 °C, is able to assimilate aromatic hydrocarbons (toluene, mineral oil, n-hexadecane), and shows abundant growth with selected neurotransmitters (acetylcholine, gamma-aminobutyric acid, glycine, glutamate, and dopamine) as sole carbon sources. We have for the first time demonstrated the effect of E. dermatitidis on neuroblastoma cell model SH-SY5Y. Aqueous and organic extracts of E. dermatitidis biomass reduced SH-SY5Y viability by 51% and 37%, respectively. Melanized extracellular vesicles (EVs) prepared from this strain reduced viability of the SH-SY5Y to 21%, while non-melanized EVs were considerably less neurotoxic (79% viability). We also demonstrated direct interactions of E. dermatitidis with SH-SY5Y by scanning electron and confocal fluorescence microscopy. The observed invasion and penetration of neuroblastoma cells by E. dermatitidis hyphae presumably causes the degradation of most neuroblastoma cells in only three days. This may represent a so far unknown indirect or direct cause for the development of some neurodegenerative diseases such as Alzheimer’s.

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Section: Discussionsupporting

confidence: 53%

The Neurotropic Black Yeast Exophiala dermatitidis Induces Neurocytotoxicity in Neuroblastoma Cells and Progressive Cell Death

Lavrin

Konte

Kostanjšek

et al. 2020

Cells

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“…In our research, 11 genes belonged to the Barwin family (Table 1) known elicitor cerato-platanin of fungi (Pazzagli et al, 1999), which are more than that found by Bruce et al (2014), who found only one CSEP that was associated with Barwin through performing transcriptome analysis on 6 P. triticina races and obtained 532 CSEPs. It has also been reported that proteins containing this domain promoted the successful colonization of C. neoformans in the lungs of mammals (Camacho et al, 2019). In addition, these candidate effector proteins included other family domains (Table 1), such as the ribonuclease family, the peptidase family, the aldehyde dehydrogenase family, the Bowman-Birk serine protease inhibitor family, the Ras family, etc.…”

Section: Cseps Of P Triticina May Confer Many Functionsmentioning

confidence: 98%

Predicating the Effector Proteins Secreted by Puccinia triticina Through Transcriptomic Analysis and Multiple Prediction Approaches

Zhang

Wei

et al. 2020

Front. Microbiol.

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Wheat leaf rust caused by Puccinia triticina is one of the most common and serious diseases in wheat production. The constantly changing pathogens overcome the plant resistance to P. triticina. Plant pathogens secrete effector proteins that alter the structure of the host cell, interfere plant defenses, or modify the physiology of plant cells. Therefore, the identification of effector proteins is critical to reveal the pathogenic mechanism. We used SignalP v4.1, TargetP v1.1, TMHMM v2.0, and EffectorP v2.0 to screen the candidate effector proteins in P. triticina isolates-KHTT, JHKT, and THSN. As a result, a total of 635 candidate effector proteins were obtained. Structural analysis showed that effector proteins were small in size (50AA to 422AA) and of diverse sequences, and the conserved sequential elements or clear common elements were not involved, regardless of their secretion from the pathogen to the host. There were 427 candidate effector proteins that contain more than or equal to 4 cysteine residues, and 339 candidate effector proteins contained the known motifs. Sixteen families, 9 domains, and 53 other known functional types were found in 186 candidate effector proteins using the Pfam search. Three novel motifs were found by MEME. Heterogeneous expression system was performed to verify the functions of 30 candidate effectors by inhibiting the programmed cell death (PCD) induced by BAX (the mouse-apoptotic gene elicitor) on Nicotiana benthamiana. Hypersensitive response (HR) can be induced by the six effectors in the wheat leaf rust resistance near isogenic lines, and this would be shown by the method of transient expression through Agrobacterium tumefaciens infiltration. The quantitative reverse transcription PCR (qRT-PCR) analysis of 14 candidate effector proteins secreted after P. triticina inoculation showed that the tested effectors displayed different expression patterns in different stages, suggesting that they may be involved in the wheat-P. triticina interaction. The results showed that the prediction of P. triticina effector proteins based on transcriptomic analysis and multiple bioinformatics software is effective and more accurate, laying the foundation of revealing the pathogenic mechanism of Pt and controlling disease.

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“…In C. neoformans , chitinases have been reported to be essential for sexual development but not vegetative growth and asexual reproduction ( Baker et al, 2009 ). Furthermore, it has been suggested that cryptococcal chitinases are indirectly enrolled in modifications of the melanin scaffold (i.e., through the regular cell-wall remodeling activity) that lead to the detachment of melanin granules detachment from the cell wall ( Camacho et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

A Plumieridine-Rich Fraction From Allamanda polyantha Inhibits Chitinolytic Activity and Exhibits Antifungal Properties Against Cryptococcus neoformans

et al. 2020

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Cryptococcosis is a fungal infection caused mainly by the pathogenic yeasts Cryptococcus neoformans and Cryptococcus gattii . The infection initiates with the inhalation of propagules that are then deposited in the lungs. If not properly treated, cryptococci cells can disseminate and reach the central nervous system. The current recommended treatment for cryptococcosis employs a three-stage regimen, with the administration of amphotericin B, flucytosine and fluconazole. Although effective, these drugs are often unavailable worldwide, can lead to resistance development, and may display toxic effects on the patients. Thus, new drugs for cryptococcosis treatment are needed. Recently, an iridoid named plumieridine was found in Allamanda polyantha seed extract; it exhibited antifungal activity against C. neoformans with a MIC of 250 μg/mL. To address the mode of action of plumieridine, several in silico and in vitro experiments were performed. Through a ligand-based a virtual screening approach, chitinases were identified as potential targets. Confirmatory in vitro assays showed that C. neoformans cell-free supernatant incubated with plumieridine displayed reduced chitinase activity, while chitinolytic activity was not inhibited in the insoluble cell fraction. Additionally, confocal microscopy revealed changes in the distribution of chitooligomers in the cryptococcal cell wall, from a polarized to a diffuse cell pattern state. Remarkably, further assays have shown that plumieridine can also inhibit the chitinolytic activity from the supernatant and cell-free extracts of bacteria, insect and mouse-derived macrophage cells (J774.A1). Together, our results suggest that plumieridine can be a broad-spectrum chitinase inhibitor.

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The structural unit of melanin in the cell wall of the fungal pathogen Cryptococcus neoformans

Cited by 91 publications

References 95 publications

The Neurotropic Black Yeast Exophiala dermatitidis Induces Neurocytotoxicity in Neuroblastoma Cells and Progressive Cell Death

The Neurotropic Black Yeast Exophiala dermatitidis Induces Neurocytotoxicity in Neuroblastoma Cells and Progressive Cell Death

Predicating the Effector Proteins Secreted by Puccinia triticina Through Transcriptomic Analysis and Multiple Prediction Approaches

A Plumieridine-Rich Fraction From Allamanda polyantha Inhibits Chitinolytic Activity and Exhibits Antifungal Properties Against Cryptococcus neoformans

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