-
Molecules (Basel, Switzerland) Dec 2023Biotransformation of ursonic acid () by two fungal strains CGMCC 3.5324 and CGMCC 3.407 yielded thirteen new compounds (, , -, and -), along with five recognized ones....
Biotransformation of ursonic acid () by two fungal strains CGMCC 3.5324 and CGMCC 3.407 yielded thirteen new compounds (, , -, and -), along with five recognized ones. The structural details of new compounds were determined through spectroscopic examination (NMR, IR, and HR-MS) and X-ray crystallography. Various modifications, including hydroxylation, epoxidation, lactonization, oxygen introduction, and transmethylation, were identified on the ursane core. Additionally, the anti-neuroinflammatory efficacy of these derivatives was assessed on BV-2 cells affected by lipopolysaccharides. It was observed that certain methoxylated and epoxylated derivatives (, , and ) showcased enhanced suppressive capabilities, boasting IC values of 8.2, 6.9, and 5.3 μM. Such ursonic acid derivatives might emerge as potential primary molecules in addressing neurodegenerative diseases.
Topics: Aspergillus ochraceus; Aspergillus oryzae; Crystallography, X-Ray; Biotransformation
PubMed: 38138433
DOI: 10.3390/molecules28247943 -
Medical Mycology Journal 2022Aspergillosis is a major fungal infection in humans and animals. Penguins (Order Spheniscidae) are particularly susceptible to aspergillosis, and aspergillosis in...
Aspergillosis is a major fungal infection in humans and animals. Penguins (Order Spheniscidae) are particularly susceptible to aspergillosis, and aspergillosis in captive penguins is presently a major problem. We were faced with the challenge of combating aspergillosis in an aquarium. As a solution, we organized a multidisciplinary aspergillosis control team, including a medical and veterinary mycologist. Since Aspergillus, including Aspergillus fumigatus, is abundant in soil, we thought it necessary to minimize contact between captive penguins and soil to prevent aspergillosis. As a countermeasure, we stopped using a route for outdoor penguin marches where the soil was exposed. Additionally, after outdoor penguin marches, the feet of penguins were washed with seawater to avoid bringing soil into the rearing facility for penguins. Furthermore, since A. fumigatus was detected on several spots in the environment of the rearing facility by swab analysis, we cleaned and sanitized the rearing facility with 0.02% sodium hypochlorite and hot water. As a result of the above measures, there has been no incidence of aspergillosis in captive penguins since 2016. These results show that our preventive measures are working well. As shown here, we presented an example of how the multidisciplinary control team, which included a mycologist, successfully implemented preventive measures against aspergillosis. Due to changes in the rearing environment and the impact of global warming on penguins, it is expected that the role of mycologists in aspergillosis control will expand in the future.
Topics: Animals; Aspergillosis; Aspergillus; Aspergillus fumigatus; Soil; Spheniscidae
PubMed: 35650070
DOI: 10.3314/mmj.22.002 -
BMC Microbiology Feb 2020Invasive aspergillosis is a fungal infection that occurs mainly in immunocompromised patients. It is responsible for a high degree of mortality and is invariably...
BACKGROUND
Invasive aspergillosis is a fungal infection that occurs mainly in immunocompromised patients. It is responsible for a high degree of mortality and is invariably unresponsive to conventional antifungal treatments. Histone deacetylase inhibitors can affect the cell cycle, apoptosis and differentiation. The histone deacetylase inhibitor vorinostat (SAHA) has recently received approval for the treatment of cutaneous T cell lymphoma. Here, we investigated the interactions of SAHA and itraconazole, voriconazole, and posaconazole against Aspergillus spp. in vitro using both planktonic cells and biofilms.
RESULTS
We investigated 20 clinical strains using broth microdilution checkerboard methods. The results showed synergy between SAHA and itraconazole, voriconazole, and posaconazole against 60, 40, and 25% of tested isolates of planktonic Aspergillus spp., respectively. Similar synergy was also observed against Aspergillus biofilms. The expression of the azole-associated multidrug efflux pumps MDR1, MDR2, MDR3 and MDR4, as well as that of HSP90, was measured by RT-PCR. The results indicated that the molecular mechanism of the observed synergistic effects in Aspergillus fumigatus may be partly associated with dampened expression of the efflux pump genes and, furthermore, that HSP90 suppression may be a major contributor to the observed synergistic effects of the drugs.
CONCLUSIONS
SAHA has potential as a secondary treatment to enhance the effects of azoles against both biofilm and planktonic cells of Aspergillus spp. in vitro. This effect occurs mostly by inhibition of HSP90 expression.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Aspergillus; Azoles; Biofilms; Drug Synergism; Gene Expression Regulation; HSP90 Heat-Shock Proteins; Itraconazole; Microbial Sensitivity Tests; Plankton; Triazoles; Voriconazole; Vorinostat; ATP-Binding Cassette Sub-Family B Member 4
PubMed: 32028887
DOI: 10.1186/s12866-020-1718-x -
Toxins Jan 2020Traditional medicinal herbs are widely used and may be contaminated with mycotoxigenic fungi during cultivation, harvesting, and storage, causing spoilage and mycotoxin...
Traditional medicinal herbs are widely used and may be contaminated with mycotoxigenic fungi during cultivation, harvesting, and storage, causing spoilage and mycotoxin production. We evaluated the predominant mycoflora and extent of mycotoxin contaminations in 48 contaminated samples of 13 different medicinal herbs. In total, 70.8% of herbs were slightly contaminated with aflatoxins (<5 μg kg). radix samples contained ochratoxin A (OTA) (360-515 μg kg), and Scutellariae radix samples contained OTA (49-231 μg kg) and citrinin (15-53 μg kg). Forty samples (83.3%) contained fungal contamination. Sixty-nine strains were characterized via morphological and molecular identification. The predominant mycoflora comprised four genera, spp. (26.1%), spp. (24.6%), spp. (14.5%), and spp. (11.6%). Aflatoxins, OTA, and citrinin were detected in 37 cultures by high-performance liquid chromatography-tandem mass spectrometry. Approximately 21.6% of and isolates produced mycotoxins. One strain isolated from radix synthesized citrinin. Multiplex PCR analysis showed that three strains harbored aflatoxin biosynthesis genes. One strain isolated from fructus produced AFB and AFB. To the best of our knowledge, the citrinin production by and was first reported in this study, which poses a potential risk of mycotoxin contamination in medicinal herbs.
Topics: Aflatoxins; Aspergillus; Aspergillus flavus; Citrinin; Food Contamination; Food Microbiology; Fungi; Mycotoxins; Ochratoxins; Penicillium; Plants, Medicinal
PubMed: 31947869
DOI: 10.3390/toxins12010030 -
Molecules (Basel, Switzerland) Apr 2022Fungi comprise the second most species-rich organism group after that of insects. Recent estimates hypothesized that the currently reported fungal species range from 3.5... (Review)
Review
Fungi comprise the second most species-rich organism group after that of insects. Recent estimates hypothesized that the currently reported fungal species range from 3.5 to 5.1 million types worldwide. Fungi can grow in a wide range of habitats, from the desert to the depths of the sea. Most develop in terrestrial environments, but several species live only in aquatic habitats, and some live in symbiotic relationships with plants, animals, or other fungi. Fungi have been proved to be a rich source of biologically active natural products, some of which are clinically important drugs such as the β-lactam antibiotics, penicillin and cephalosporin, the immunosuppressant, cyclosporine, and the cholesterol-lowering drugs, compactin and lovastatin. Given the estimates of fungal biodiversity, it is easy to perceive that only a small fraction of fungi worldwide have ever been investigated regarding the production of biologically valuable compounds. Traditionally, fungi are classified primarily based on the structures associated with sexual reproduction. Thus, the genus (Family Trichocomaceae) is the telemorphic (sexual state) of the section known as , which produces both a sexual state with ascospores and an asexual state with conidiospores, while the species produces only conidiospores. However, according to the Melbourne Code of nomenclature, only the genus name is to be used for both sexual and asexual states. Consequently, the genus name was no longer to be used after 1 January 2013. Nevertheless, the genus name is still used for the fungi that had already been taxonomically classified before the new rule was in force. Another aspect is that despite the small number of species (23 species) in the genus and although less than half of them have been investigated chemically, the chemical diversity of this genus is impressive. Many chemical classes of compounds, some of which have unique scaffolds, such as indole alkaloids, peptides, meroterpenes, and polyketides, have been reported from its terrestrial, marine-derived, and endophytic species. Though the biological and pharmacological activities of a small fraction of the isolated metabolites have been investigated due to the available assay systems, they exhibited relevant biological and pharmacological activities, such as anticancer, antibacterial, antiplasmodial, lipid-lowering, and enzyme-inhibitory activities.
Topics: Animals; Anti-Bacterial Agents; Aspergillus; Biological Products; Fungi; Neosartorya; Polyketides
PubMed: 35408769
DOI: 10.3390/molecules27072351 -
Journal of Clinical Microbiology Feb 2022Aspergillus antibody testing is key for the clinical diagnosis of chronic pulmonary aspergillosis (CPA) with high sensitivity. However, false-negative results in...
Aspergillus antibody testing is key for the clinical diagnosis of chronic pulmonary aspergillosis (CPA) with high sensitivity. However, false-negative results in patients with CPA might be obtained, depending on the Aspergillus species. The aim of this study was to investigate which factors are associated with false-negative results in Aspergillus precipitin tests and whether the sensitivity of precipitin tests in CPA is influenced by Aspergillus fumigatus and non- Aspergillus species. Between February 2012 and December 2020, 116 consecutive antifungal treatment-naive patients with CPA were identified and included in this retrospective chart review. Aspergillus species isolated from the respiratory tract of patients were identified by DNA sequencing. Characteristics of patients with positive and negative results for Aspergillus precipitin tests were compared. The sensitivity of the Aspergillus precipitin tests was compared between patients with A. fumigatus-associated CPA and non- Aspergillus-associated CPA. A non- Aspergillus species was the only factor significantly associated with negative Aspergillus precipitin test results in patients with CPA in the multivariate analysis (hazard ratio, 8.3; 95% confidence interval, 3.2 to 22.1; < 0.0001). The positivity of the Aspergillus precipitin test for patients with non- Aspergillus-associated CPA was lower than that for patients with A. fumigatus-associated CPA (84.8% versus 37.9%; < 0.0001). These results revealed that the presence of non- Aspergillus-associated CPA should be considered with a negative Aspergillus precipitin test; this finding may prevent diagnostic delay or misdiagnosis for CPA.
Topics: Aspergillus; Aspergillus fumigatus; Delayed Diagnosis; Humans; Precipitin Tests; Pulmonary Aspergillosis; Retrospective Studies
PubMed: 34878803
DOI: 10.1128/JCM.02018-21 -
Microbial Cell Factories Mar 2020Caffeine, theobromine and theophylline are main purine alkaloid in tea. Theophylline is the downstream metabolite and it remains at a very low level in Camellia...
BACKGROUND
Caffeine, theobromine and theophylline are main purine alkaloid in tea. Theophylline is the downstream metabolite and it remains at a very low level in Camellia sinensis. In our previous study, Aspergillus sydowii could convert caffeine into theophylline in solid-state fermentation of pu-erh tea through N-demethylation. In this study, tea-derived fungi caused theophylline degradation in the solid-state fermentation. The purpose of this study is identify and isolate theophylline-degrading fungi and investigate their application in production of methylxanthines with theophylline as feedstock through microbial conversion.
RESULTS
Seven tea-derived fungi were collected and identified by ITS, β-tubulin and calmodulin gene sequences, Aspergillus ustus, Aspergillus tamarii, Aspergillus niger and A. sydowii associated with solid-state fermentation of pu-erh tea have shown ability to degrade theophylline in liquid culture. Particularly, A. ustus and A. tamarii could degrade theophylline highly significantly (p < 0.01). 1,3-dimethyluric acid, 3-methylxanthine, 3-methyluric acid, xanthine and uric acid were detected consecutively by HPLC in A. ustus and A. tamarii, respectively. The data from absolute quantification analysis suggested that 3-methylxanthine and xanthine were the main degraded metabolites in A. ustus and A. tamarii, respectively. 129.48 ± 5.81 mg/L of 3-methylxanthine and 159.11 ± 10.8 mg/L of xanthine were produced by A. ustus and A. tamarii in 300 mg/L of theophylline liquid medium, respectively.
CONCLUSIONS
For the first time, we confirmed that isolated A. ustus, A. tamarii degrade theophylline through N-demethylation and oxidation. We were able to biologically produce 3-methylxanthine and xanthine efficiently from theophylline through a new microbial synthesis platform with A. ustus and A. tamarii as appropriate starter strains.
Topics: Aspergillus; Biotransformation; Fermentation; Theophylline; Xanthine; Xanthines
PubMed: 32192512
DOI: 10.1186/s12934-020-01333-0 -
Microbial Biotechnology Jun 2022Filamentous fungi produce a wide variety of enzymes in order to efficiently degrade plant cell wall polysaccharides. The production of these enzymes is controlled by...
Filamentous fungi produce a wide variety of enzymes in order to efficiently degrade plant cell wall polysaccharides. The production of these enzymes is controlled by transcriptional regulators, which also control the catabolic pathways that convert the released monosaccharides. Two transcriptional regulators, GalX and GalR, control d-galactose utilization in the model filamentous fungus Aspergillus nidulans, while the arabinanolytic regulator AraR regulates l-arabinose catabolism. d-Galactose and l-arabinose are commonly found together in polysaccharides, such as arabinogalactan, xylan and rhamnogalacturonan I. Therefore, the catabolic pathways that convert d-galactose and l-arabinose are often also likely to be active simultaneously. In this study, we investigated the interaction between GalX, GalR and AraR in d-galactose and l-arabinose catabolism. For this, we generated single, double and triple mutants of the three regulators, and analysed their growth and enzyme and gene expression profiles. Our results clearly demonstrated that GalX, GalR and AraR co-regulate d-galactose catabolism in A. nidulans. GalX has a prominent role on the regulation of genes of d-galactose oxido-reductive pathway, while AraR can compensate for the absence of GalR and/or GalX.
Topics: Arabinose; Aspergillus nidulans; Galactose; Gene Expression Regulation, Fungal; Polysaccharides; Transcription Factors
PubMed: 35213794
DOI: 10.1111/1751-7915.14025 -
Current Opinion in Microbiology Oct 2021Filamentous fungi Aspergillus and Fusarium species are major causes of visual impairment and blindness in immune competent individuals. Once conidia penetrate the... (Review)
Review
Filamentous fungi Aspergillus and Fusarium species are major causes of visual impairment and blindness in immune competent individuals. Once conidia penetrate the corneal epithelium and enter the stroma, they undergo germination, and exposure of cell wall components induces a pronounced neutrophil-rich cellular infiltrate. In this review, we discuss Aspergillus and novel Fusarium virulence factors that are required for corneal infection, and describe the multiple functions of neutrophils in limiting hyphal growth in the cornea. This review will also discuss the role of neutrophils as an important source of cytokines in fungal keratitis, and highlight recent studies identifying unique characteristics of neutrophil secretion of IL-1α and IL-1β.
Topics: Animals; Aspergillus; Aspergillus fumigatus; Fusarium; Humans; Keratitis; Mice; Mice, Inbred C57BL; Neutrophils
PubMed: 34419783
DOI: 10.1016/j.mib.2021.07.018 -
Essays in Biochemistry Jul 2021The filamentous ascomycete fungus Aspergillus niger is a prolific secretor of organic acids, proteins, enzymes and secondary metabolites. Throughout the last century,... (Review)
Review
The filamentous ascomycete fungus Aspergillus niger is a prolific secretor of organic acids, proteins, enzymes and secondary metabolites. Throughout the last century, biotechnologists have developed A. niger into a multipurpose cell factory with a product portfolio worth billions of dollars each year. Recent technological advances, from genome editing to other molecular and omics tools, promise to revolutionize our understanding of A. niger biology, ultimately to increase efficiency of existing industrial applications or even to make entirely new products. However, various challenges to this biotechnological vision, many several decades old, still limit applications of this fungus. These include an inability to tightly control A. niger growth for optimal productivity, and a lack of high-throughput cultivation conditions for mutant screening. In this mini-review, we summarize the current state-of-the-art for A. niger biotechnology with special focus on organic acids (citric acid, malic acid, gluconic acid and itaconic acid), secreted proteins and secondary metabolites, and discuss how new technological developments can be applied to comprehensively address a variety of old and persistent challenges.
Topics: Aspergillus niger; Biotechnology; Citric Acid; Gene Editing
PubMed: 33955461
DOI: 10.1042/EBC20200139