gliotoxin

C. elegans numr-1/2 (<u>nu</u>clear-localized <u>m</u>etal-<u>r</u>esponsive) is an identical gene pair encoding a nuclear protein previously shown to be activated by cadmium and disruption of the integrator RNA metabolism complex. We took a chemical genetic approach to further characterize regulation of this novel metal response by screening 41,716 compounds and extracts for numr-1p::GFP activation. The most potent activator was chaetocin, a fungal 3,6-epidithiodiketopiperazine (ETP) with promising anticancer activity...

Gliotoxin (GT) belongs to the epipolythiodioxopiperazine (ETP) family, which is considered a crucial virulence determinant among the secondary metabolites produced by Aspergillus fumigatus. The metabolites are commonly found in food and feed, contributing to the invasion and immune escape of Aspergillus fumigatus, thereby posing a significant threat to the health of livestock, poultry, and humans. Heterophil extracellular traps (HETs), a novel form of innate immune defense, have been documented in the chicken's innate immune systems for capturing and eliminating invading microbes...

Fungi biosynthesize diverse secondary metabolites, small organic bioactive molecules with key roles in fungal ecology. Fungal secondary metabolites are often encoded by physically clustered genes known as biosynthetic gene clusters (BGCs). Fungi in the genus Penicillium produce a cadre of secondary metabolites, some of which are useful (e.g., the antibiotic penicillin and the cholesterol-lowering drug mevastatin) and others harmful (e.g., the mycotoxin patulin and the immunosuppressant gliotoxin) to human affairs...

Fungal pathogens exhibit extensive strain heterogeneity, including variation in virulence. Whether closely related non-pathogenic species also exhibit strain heterogeneity remains unknown. Here, we comprehensively characterized the pathogenic potentials (i.e., the ability to cause morbidity and mortality) of 16 diverse strains of Aspergillus fischeri , a non-pathogenic close relative of the major pathogen Aspergillus fumigatus . In vitro immune response assays and in vivo virulence assays using a mouse model of pulmonary aspergillosis showed that A...

Mucormycosis is receiving much more attention because of its high morbidity and extremely high mortality rate in immunosuppressed populations. In this study, we isolated a Cunnignhamella bertholletiae Z2 strain from a skin lesion of a 14 year, 9 months old girl with acute lymphoblastic leukemia who die of infection from the Z2 strain. Genome sequencing was performed after isolation and amplification of the Z2 strain to reveal potential virulence factors and pathogenic mechanisms. The results showed that the genome size of the Z2 strain is 30...

Aspergillus fumigatus is the leading cause of aspergillosis, associated with high mortality rates, particularly in immunocompromised individuals. In search of novel genetic targets against aspergillosis, we studied the WOPR transcription factor OsaA. The deletion of the osaA gene resulted in colony growth reduction. Conidiation is also influenced by osaA ; both osaA deletion and overexpression resulted in a decrease in spore production. Wild-type expression levels of osaA are necessary for the expression of the conidiation regulatory genes brlA , abaA , and wetA ...

BACKGROUND: Emerging evidence has demonstrated the impact of psychological stress on intestinal microbiota, however, the precise mechanisms are not fully understood. Enteric glia, a unique type of peripheral glia found within the enteric nervous system (ENS), play an active role in enteric neural circuits and have profound effects on gut functions. In the present study, we tested the hypothesis that enteric glia are involved in the alterations in the intestinal microflora and barrier induced by chronic water-avoidance stress (WAS) in the gut...

In the present research, the antiproliferative properties of Gliotoxin, which is obtained from marine fungus and thought to be a promising metabolite, on MCF-7 and MDA-MB-231 breast cancer cells, which have different molecular subtypes, were evaluated. Different cell kinetic parameters were employed for this aim. In experiments, cell viability, cell index, mitotic index, BrdU labeling index, and apoptotic index were assessed. Gliotoxin concentrations of 1.5625 µM, 3.125 µM, and 6.25 µM were used in studies for both cell lines...

In nature, the formation of specialized (secondary) metabolites is associated with the late stages of fungal development. Enzymes involved in the biosynthesis of secondary metabolites in fungi are located in distinct subcellular compartments including the cytosol, peroxisomes, endosomes, endoplasmic reticulum, different types of vesicles, the plasma membrane and the cell wall space. The enzymes traffic between these subcellular compartments and the secretion through the plasma membrane are still unclear in the biosynthetic processes of most of these metabolites...

Endophytic fungi have been recognized as a valuable source for the production of biologically active compounds with potential applications in various domains. This study aimed to isolate endophytic fungi from Ampelopsis japonica (Thunb.) Makino and assess their anti-MRSA activity. Meanwhile, chromatographic separation techniques were applied to analyze the constituents of endophytic fungal secondary metabolites. The isolate BLR24, which exhibited strong inhibition activity against MRSA, was identified as Trichoderma virens based on morphological characteristics and ITS sequence analyses...

Mycotoxins such as gliotoxin (GTX) and ochratoxin A (OTA) are secondary metabolites of Aspergillus and Penicillum found in food and feed. Both mycotoxins have shown to exert a detrimental effect on neuronal activity. The following study was carried out to elucidate the mechanisms by which GTX and OTA exert their toxicity. Non-differentiated SH-SY5Y neuronal-like cells were treated with GTX, OTA and their combinations to assess their cytotoxic effect using the MTT assay during 24, 48 and 72h of exposure. Based on the results of the cytotoxic assays, cell cycle proliferation and immunological mediators were measured by determining the production of IL-6 and TNF-α using flow cytometry and ELISA, respectively...

Aspergillus fumigatus is a saprophytic fungus that can cause a variety of human diseases known as aspergillosis. Mycotoxin gliotoxin (GT) production is important for its virulence and must be tightly regulated to avoid excess production and toxicity to the fungus. GT self-protection by GliT oxidoreductase and GtmA methyltransferase activities is related to the subcellular localization of these enzymes and how GT can be sequestered from the cytoplasm to avoid increased cell damage. Here, we show that GliT:GFP and GtmA:GFP are localized in the cytoplasm and in vacuoles during GT production...

The Mycobacterium tuberculosis (MTB) infection causes tuberculosis (TB) and has been a long-standing public-health threat. It is urgent that we discover novel antitubercular agents to manage the increased incidence of multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains of MTB and tackle the adverse effects of the first- and second-line antitubercular drugs. We previously found that gliotoxin ( 1 ), 12, 13-dihydroxy-fumitremorgin C ( 2 ), and helvolic acid ( 3 ) from the cultures of a deep-sea-derived fungus, Aspergillus sp...

AIMS: Aspergillus fungi are common members of soil microbiota. Some physiological and structural characteristics of Aspergillus species make them important participants in soil ecological processes. In this study, we aimed to evaluate the impact of 2,4-diacetylphloroglucinol (2,4-DAPG), a common metabolite of soil and rhizosphere bacteria, on the physiology of Aspergillus fumigatus. METHODS AND RESULTS: Integrated analysis using microscopy, spectrophotometry and liquid chromatography showed the following effects of 2,4-DAPG on Aspergillus physiology...

In this study, we explored the potential antidepressant-like properties of the brain-penetrant Y2 receptor (Y2R) antagonist SF-11 [N-(4-ethoxyphenyl)-4-(hydroxydiphenylmethyl)-1-piperidinecarbothioamide] in the astroglial degeneration model of depression with an emphasis on checking the possible mechanisms implicated in this antidepressant-like effect. The model of depression relies on the loss of astrocytes in the medial prefrontal cortex (mPFC) in Sprague-Dawley rats after administering the gliotoxin L-alpha-aminoadipic acid (L-AAA)...

BACKGROUND AND AIM: Several strains of Aspergillus fumigatus produce mycotoxins that affect the health and productivity of dairy cattle, and their presence in dairy cattle feed is a serious concern. This study aimed to determine the densities of A. fumigatus and gliotoxin in commercial dairy feed. MATERIALS AND METHODS: More than 60 dairy feed samples were examined for fungal contamination, specifically for A. fumigatus , using phenotypic approaches and DNA sequencing of the internal transcribed spacer ( ITS ) and β-tubulin regions...

Overcoming antimicrobial resistance represents a formidable challenge and investigating bacterial growth inhibition by fungal metabolites may yield new strategies. Although the fungal non-ribosomal peptide gliotoxin (GT) is known to exhibit antibacterial activity, the mechanism(s) of action are unknown, although reduced gliotoxin (dithiol gliotoxin; DTG) is a zinc chelator. Furthermore, it has been demonstrated that GT synergises with vancomycin to inhibit growth of Staphylococcus aureus. Here we demonstrate, without precedent, that GT-mediated growth inhibition of both Gram positive and negative bacterial species is reversed by Zn2+ or Cu2+ addition...

Fifty-seven samples of honey of different types and origins were screened for nicotine and nine mycotoxins (aflatoxin B1 , aflatoxin B2 , fusarenon X, ochratoxin A, penicillic acid, zearalenone, sterigmatocystin, gliotoxin, and patulin). The sample set consisted of monofloral, multifloral, nectar, honeydrew, cream, and artificial honey originating mainly from Poland. The physicochemical characterization of honey was performed by determining colour (by Pfund method), water content (by refractometry), total phenolics and flavonoids content (by spectrophotometry)...

Lung infection with the fungus Aspergillus fumigatus ( Af ) is a common complication in cystic fibrosis (CF) and is associated with loss of pulmonary function. We established a fungal epithelial co-culture model to examine the impact of Af infection on CF bronchial epithelial barrier function using Af strains 10AF and AF293-GFP, and the CFBE41o- cell line homozygous for the F508del mutation with (CF+CFTR ) and without (CF) normal CFTR expression. Following exposure of the epithelial surface to Af conidia, formation of germlings (early stages of fungal growth) was detected after 9-12 hours and hyphae (mature fungal growth) after 12-24 hours...

Here, a novel rapid and ultrasensitive aptamer biosensor was designed for target-induced activation of AIE effect and followed by the activation of Crispr Cas12a (LbCpf1)-mediated cleavage to achieve dual-signal detection. The prepared DNA building blocks contain the target aptamer, ssDNA-Fc, and Activator1. In this system, the activation mode was divided into two steps. First, when the target interacts with the aptamers, the DNA building blocks would be disintegrated rapidly, releasing a mass of Ac1, generating ETTC-dsDNA aggregated to produce a fluorescence signal by the AIE effect...