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BACKGROUND: Taxol, derived from Taxus trees, is a valuable natural resource for the development of anticancer drugs. Endophytic fungi from Taxus trees are a promising alternative source of Taxol. However, the impact of plant-endophytic microbial interaction on the host's Taxol biosynthesis is largely unknown. RESULTS: In the current study, the diversity of endophytic fungi in three different Taxus species was analyzed using Internal Transcribed Spacer sequencing. A total of 271 Operational Taxonomic Units (OTUs) were identified, grouping into 2 phyla, 8 classes, 16 orders, 19 families, and 19 genera. Alpha and beta diversity analysis indicated significant differences in endophytic fungal communities among the various Taxus trees. At the genus level, Alternaria and Davidiella were predominantly found in T. mairei and T. media, respectively. By utilizing a previously published dataset, a Pearson correlation analysis was conducted to predict the taxol biosynthesis-related fungal genera. Following screening, two isolates of Alternaria (L7 and M14) were obtained. Effect of inoculation with Alternaria isolates on the gene expression and metabolite accumulation of T. mairei was determined by transcriptomic and untargeted metabolomic studies. The co-inoculation assay suggests that the two Alternaria isolates may have a negative regulatory effect on taxol biosynthesis by influencing hormone signaling pathways. CONCLUSION: Our findings will serve as a foundation for advancing the production and utilization of Taxus and will also aid in screening endophytic fungi related to taxol production.
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Alternaria , Endófitos , Paclitaxel , Taxus , Taxus/microbiología , Paclitaxel/biosíntesis , Endófitos/genética , Endófitos/metabolismo , Endófitos/aislamiento & purificación , Endófitos/clasificación , Alternaria/genética , Alternaria/metabolismo , Alternaria/clasificación , Alternaria/aislamiento & purificación , Filogenia , Hongos/genética , Hongos/metabolismo , Hongos/clasificación , Hongos/aislamiento & purificación , ADN de Hongos/genética , ADN Espaciador Ribosómico/genéticaRESUMEN
INTRODUCTION: Fungi biosynthesize chemically diverse secondary metabolites with a wide range of biological activities. Natural product scientists have increasingly turned towards bioinformatics approaches, combining metabolomics and genomics to target secondary metabolites and their biosynthetic machinery. We recently applied an integrated metabologenomics workflow to 110 fungi and identified more than 230 high-confidence linkages between metabolites and their biosynthetic pathways. OBJECTIVES: To prioritize the discovery of bioactive natural products and their biosynthetic pathways from these hundreds of high-confidence linkages, we developed a bioactivity-driven metabologenomics workflow combining quantitative chemical information, antiproliferative bioactivity data, and genome sequences. METHODS: The 110 fungi from our metabologenomics study were tested against multiple cancer cell lines to identify which strains produced antiproliferative natural products. Three strains were selected for further study, fractionated using flash chromatography, and subjected to an additional round of bioactivity testing and mass spectral analysis. Data were overlaid using biochemometrics analysis to predict active constituents early in the fractionation process following which their biosynthetic pathways were identified using metabologenomics. RESULTS: We isolated three new-to-nature stemphone analogs, 19-acetylstemphones G (1), B (2) and E (3), that demonstrated antiproliferative activity ranging from 3 to 5 µM against human melanoma (MDA-MB-435) and ovarian cancer (OVACR3) cells. We proposed a rational biosynthetic pathway for these compounds, highlighting the potential of using bioactivity as a filter for the analysis of integrated-Omics datasets. CONCLUSIONS: This work demonstrates how the incorporation of biochemometrics as a third dimension into the metabologenomics workflow can identify bioactive metabolites and link them to their biosynthetic machinery.
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Vías Biosintéticas , Hongos , Metabolómica , Familia de Multigenes , Humanos , Metabolómica/métodos , Hongos/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Productos Biológicos/farmacología , Productos Biológicos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/metabolismoRESUMEN
Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies.
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ADN de Hongos , Neutropenia Febril , Huésped Inmunocomprometido , Humanos , Estudios Prospectivos , Adulto , Neutropenia Febril/microbiología , ADN de Hongos/análisis , Femenino , Masculino , Niño , Adolescente , Persona de Mediana Edad , Prevalencia , Adulto Joven , Anciano , Hongos/aislamiento & purificación , Hongos/genética , Neoplasias Hematológicas/complicaciones , Preescolar , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Fúngicas Invasoras/epidemiología , Infecciones Fúngicas Invasoras/prevención & control , Infecciones Fúngicas Invasoras/etiología , Infecciones Fúngicas Invasoras/microbiología , Antifúngicos/uso terapéuticoRESUMEN
Humic acid (HA) can substantially enhance plant growth and improve soil health. Currently, the impacts of HA concentrations variation on the development and soil quality of Panax notoginseng (Sanqi) from the forest understorey are still unclear. In this study, exogenous HA was administered to the roots of Sanqi at varying concentrations (2, 4, and 6 ml/L). Subsequently, the diversity and community structure of bacteria and fungi were assessed through high-throughput sequencing technology. The investigation further involved analyzing the interplay among the growth of sanqi, soil edaphic factors, and the microbial network stability. Our finding revealed that moderate concentrations (4 ml/L) of HA improved the fresh/dry weight of Sanqi and NO3--N levels. Compared with control, the moderate concentrations of HA had a notable impact on the bacterial and fungal communities compositions. However, there was no significant difference in the α and ß diversity of bacteria and fungi. Moreover, the abundance of beneficial bacteria (Bradyrhizobium) and harmful bacteria (Xanthobacteraceae) increased and decreased at 4 ml/L HA, respectively, while the bacterial and fungal network stability were enhanced. Structural equation model (SEM) revealed that the fresh weight of Sanqi and bacterial and fungal communities were the factors that directly affected the microbial network stability at moderate concentrations of HA. In conclusion, 4 ml/L of HA is beneficial for promoting Sanqi growth and soil quality. Our study provides a reference for increasing the yield of Sanqi and sustainable development of the Sanqi-pine agroforestry system.
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Fertilizantes , Bosques , Hongos , Sustancias Húmicas , Panax notoginseng , Microbiología del Suelo , Panax notoginseng/crecimiento & desarrollo , Sustancias Húmicas/análisis , Fertilizantes/análisis , Hongos/crecimiento & desarrollo , Hongos/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/clasificación , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/microbiología , Suelo/química , Microbiota/efectos de los fármacosRESUMEN
BACKGROUND: Although sonication is a valuable diagnostic tool for periprosthetic joint infections (PJI), it is not commonly utilized. We analyzed sonicate and intraoperative tissue culture results obtained from three hospitals to define the microbial etiology of PJIs in Korea. Furthermore, we investigated necessity of conducting regular fungal and mycobacterial cultures. METHODS: We retrospectively analyzed data for patients with suspected orthopedic-related infections between 2017 and 2022, who had undergone prostheses removal surgery. We included 193 patients with suspected PJIs, and bacterial (n = 193), fungal (n = 193), and mycobacterial (n = 186) cultures were conducted on both sonicate and intraoperative tissue samples. The diagnosis of PJI was based on the European Bone and Joint Infection Society (EBJIS) criteria. RESULTS: Out of 193 patients, 121 (62.7%) had positive sonicate cultures, while 112 (58.0%) had positive periprosthetic tissue cultures. According to EBJIS criteria, a total of 181 patients were diagnosed with PJI, and 141 patients received microbiological confirmation through sonicate fluid culture or tissue culture. Of the 181 patients, 28 were classified with acute PJI (within 3 months of implantation) and 153 with chronic PJI. Among 141 patients, staphylococci were the most common organisms, accounting for 51.8% of cases, followed by Gram-negative organisms (15.6%), fungus (8.5%), and mycobacteria (3.5%). Nearly 91.7% of fungal isolates were Candida species, which also grew in bacterial cultures. In total, 11 cases cultured positive only in tissue culture, whereas 20 cases cultured positive only in sonicate culture. The antibiotic treatment plans were adjusted according to culture results. CONCLUSIONS: Utilizing sonicate culture has greatly assisted in identifying pathogens responsible for chronic indolent PJIs, allowing suitable antimicrobial treatment. Based on few cases involving non-Candida and mycobacterial infections, it appears that routine fungal and mycobacterial cultures may not be necessary.
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Hongos , Infecciones Relacionadas con Prótesis , Humanos , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Relacionadas con Prótesis/diagnóstico , Masculino , Femenino , Anciano , República de Corea/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Hongos/aislamiento & purificación , Sonicación , Mycobacterium/aislamiento & purificación , Mycobacterium/efectos de los fármacos , Adulto , Anciano de 80 o más AñosRESUMEN
Mold infestations in buildings pose significant challenges to human health, affecting both private residences and hospitals. While molds commonly trigger asthma and allergies in the immunocompetent, they can cause life-threatening diseases in the immunocompromised. Currently, there is an unmet need for new strategies to reduce or prevent mold infestations. Far-UVC technology can inactivate microorganisms while remaining safe for humans. This study investigates the inhibitory efficacy of far-UVC light at 222 nm on the growth of common mold-producing fungi, specifically Penicillium candidum, when delivered in low-dose on-off duty cycles, a configuration consistent with its use in real-world settings. The inhibitory effect of the low-dose duty cycles was assessed on growth induced by i) an adjacent spore-producing P. candidum donor and ii) P. candidum spores seeded directly onto agar plates. In both setups, the far-UVC light significantly inhibited both vertical and horizontal growth of P. candidum, even when the UV doses were below the Threshold Value Limit of 23 mJ/cm2. These results suggest that far-UVC light holds the potential to improve indoor air quality by reducing or preventing mold growth, also when people are present.
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Penicillium , Rayos Ultravioleta , Penicillium/crecimiento & desarrollo , Penicillium/efectos de la radiación , Esporas Fúngicas/efectos de la radiación , Esporas Fúngicas/crecimiento & desarrollo , Hongos/efectos de la radiación , Hongos/crecimiento & desarrollo , Humanos , Contaminación del Aire Interior/prevención & control , Contaminación del Aire Interior/análisis , Valores Limites del UmbralRESUMEN
Chalcones are intermediate products in the biosynthesis of flavonoids, which possess a wide range of biological properties, including antimicrobial and anticancer activities. The introduction of a chlorine atom and the glucosyl moiety into their structure may increase their bioavailability, bioactivity, and pharmacological use. The combined chemical and biotechnological methods can be applied to obtain such compounds. Therefore, 2-chloro-2'-hydroxychalcone and 3-chloro-2'-hydroxychalcone were synthesized and biotransformed in cultures of two strains of filamentous fungi, i.e. Isaria fumosorosea KCH J2 and Beauveria bassiana KCH J1.5 to obtain their novel glycosylated derivatives. Pharmacokinetics, drug-likeness, and biological activity of them were predicted using cheminformatics tools. 2-Chloro-2'-hydroxychalcone, 3-chloro-2'-hydroxychalcone, their main glycosylation products, and 2'-hydrochychalcone were screened for antimicrobial activity against several microbial strains. The growth of Escherichia coli 10,536 was completely inhibited by chalcones with a chlorine atom and 3-chlorodihydrochalcone 2'-O-ß-D-(4â³-O-methyl)-glucopyranoside. The strain Pseudomonas aeruginosa DSM 939 was the most resistant to the action of the tested compounds. However, chalcone aglycones and glycosides with a chlorine atom almost completely inhibited the growth of bacteria Staphylococcus aureus DSM 799 and yeast Candida albicans DSM 1386. The tested compounds had different effects on lactic acid bacteria depending on the tested species. In general, chlorinated chalcones were more effective in the inhibition of the tested microbial strains than their unchlorinated counterparts and aglycones were a little more effective than their glycosides.
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Antiinfecciosos , Biotransformación , Chalconas , Cloro , Pruebas de Sensibilidad Microbiana , Chalconas/química , Chalconas/farmacología , Chalconas/síntesis química , Cloro/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/síntesis química , Beauveria/metabolismo , Hongos/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrolloRESUMEN
Eupenifeldin (1) is a fungal secondary metabolite possessing bis-tropolone moieties that demonstrates nanomolar cytotoxic activity against a number of cancer cell types. As a potential anticancer lead, this meroterpenoid was used to access 29 semisynthetic analogues via functionalization of the reactive hydroxy groups of the bis-tropolones. A series of ester (2-6), carbonate (7-8), sulfonate (9-16), carbamate (17-20), and ether (21-30) analogues of 1 were generated via 22 reactions. Most of these compounds were disubstituted, produced via functionalization of both of the tropolonic hydroxy moieties, although three mono-functionalized analogues (6, 8, and 24) and one tri-functionalized analogue (3) were also obtained. The cytotoxic activities of 1-30 were evaluated against human melanoma and ovarian cancer cell lines (i.e., MDA-MB-435 and OVCAR3, respectively). Ester and carbonate analogues of 1 (i.e., 2-8) maintained cytotoxicity at the nanomolar level, and the greatest improvement in aqueous solubility came from the monosuccinate analogue (6), which was acylated on the secondary hydroxy at the 11 position.
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Antineoplásicos , Tropolona , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Hongos/efectos de los fármacos , Hongos/metabolismo , Estructura Molecular , Relación Estructura-Actividad , Tropolona/química , Tropolona/farmacología , Tropolona/análogos & derivados , Tropolona/síntesis química , Arilsulfonatos/síntesis química , Arilsulfonatos/química , Arilsulfonatos/farmacologíaRESUMEN
Inoculation is widely used in composting to improve the mineralization process, however, the link of fungal inoculant to humification is rarely proposed. The objective of this study was to investigate the effect of compound fungal inoculation on humification process and fungal community dynamics in corn straw composting with two different kinds of nitrogen sources [pig manure (PM) and urea (UR)]. Structural equation modeling and random forest analysis were conducted to identify key fungi and explore the fungi-mediated humification mechanism. Results showed that fungal inoculation increased the content of humic acids in PM and UR by 71.76 % and 53.01 % compared to control, respectively. High-throughput sequencing indicated that there were more key fungal genera for lignin degradation in PM especially in the later stage of composting, but a more complex fungal (genera) connections with lower humification degree was found in UR. Network analysis and random forest suggested that inoculation promoted dominant genus such as Coprinus, affecting lignocellulose degradation. Structural equation modeling indicated that fungal inoculation could promote humification by direct pathway based on lignin degradation and indirect pathway based on stimulating the indigenous microbes such as Scedosporiu and Coprinus for the accumulation of carboxyl and polyphenol hydroxyl groups. In summary, fungal inoculation is suitable to be used combining with complex nitrogen source such as pig manure in straw composting.
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Compostaje , Hongos , Sustancias Húmicas , Estiércol , Nitrógeno , Zea mays , Sustancias Húmicas/análisis , Nitrógeno/análisis , Estiércol/microbiología , Microbiología del Suelo , Animales , Porcinos , Lignina/metabolismoRESUMEN
BACKGROUND: Keratomycosis is a form of infectious keratitis, an infection of the cornea, which is caused by fungi. This disease is a leading cause of ocular morbidity globally with at least 60 % of the affected individuals becoming monocularly blind. OBJECTIVE: This bibliometric analysis aimed to comprehensively assess the existing body of literature, providing insights of the evolution of keratomycosis research by identifying key themes and research gaps. METHODS: This work used the modeling method Latent Dirichlet Allocation (LDA) to identify and interpret scientific information on topics concerning existing categories in a set of documents. The HJ-Biplot method was also used to determine the relationship between the analyzed topics, taking into consideration the years under study. RESULTS: This bibliometric analysis was performed on a total of 2,599 scientific articles published between 1992 and 2022. The five leading countries with more scientific production and citations on keratomycosis were The United States of America, followed by India, China, United Kingdom and Australia. The top five topics studied were Case Reports and Corneal Infections, which exhibited a decreasing trend; followed by Penetrating Keratoplasty and Corneal Surgery, Ocular Effects of Antifungal Drugs, Gene Expression and Inflammatory Response in the Cornea and Patient Data which have been increasing throughout the years. However Filamentous Fungi and Specific Pathogens, and Antifungal Therapies research has been decreasing in trend. CONCLUSION: Additional investigation into innovative antifungal drug therapies is crucial for proactively tackling the potential future resistance to antifungal agents in scientific writing.
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Bibliometría , Infecciones Fúngicas del Ojo , Queratitis , Humanos , Queratitis/microbiología , Infecciones Fúngicas del Ojo/microbiología , Antifúngicos/uso terapéutico , Salud Global , Hongos/clasificación , Hongos/aislamiento & purificación , Córnea/microbiologíaRESUMEN
Black carbon (BC) formed after straw burning remains in farmland soil and coexists with plastic mulch film (PMF) debris. It is unclear how BC influences soil multifunctionality in the presence of PMF debris. In this study, we determined the joint effects of BC and PMF debris on soil biochemical properties and microbial communities. We conducted a soil microcosm experiment by adding BC formed by direct burning of wheat straw and PMF debris (polyethylene (PE) and biodegradable PMF (BP)) into soil at the dosages of 1 %, and soils were sampled on the 15th, 30th, and 100th day of soil incubation for high-throughput sequencing. The results showed that the degradation of PMF debris was accompanied by the release of microplastics (MPs). BC decreased NH4+-N (PE: 68.63 %; BP: 58.97 %) and NO3--N (PE: 12.83 %; BP: 51.37 %) and increased available phosphorus (AP) (PE: 79.12 %; BP: 26.09 %) in soil containing PMF debris. There were significant differences in enzyme activity among all the treatments. High-throughput sequencing indicated that BC reduced bacterial and fungal richness and fungal diversity in PMF debris-exposed soil, whereas PMF debris and BC resulted in significant changes in the proportion of dominant phyla and genera of bacteria and fungi, which were affected by incubation time. Furthermore, BC affected microorganisms by influencing soil properties, and pH and N content were the main influencing factors. In addition, FAPRPTAX analysis indicated that BC and PMF debris affected soil C and N cycling. These findings provide new insights into the response of soil multifunctionality to BC and PMF debris.
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Bacterias , Hongos , Plásticos , Microbiología del Suelo , Contaminantes del Suelo , Suelo , Triticum , Suelo/química , Plásticos/análisis , Contaminantes del Suelo/análisis , Bacterias/clasificación , Hollín/análisis , Microbiota , MicobiomaRESUMEN
BACKGROUND: In Chinese Pharmacopeia, Picrasma quassioides (PQ) stems and leaves are recorded as Kumu with antimicrobial, anti-cancer, anti-parasitic effects, etc. However, thick stems are predominantly utilized as medicine in many Asian countries, with leaves rarely used. By now, the phytochemistry and bioactivity of PQ leaves are not well investigated. METHODS: An Orbitrap Elite mass spectrometer was employed to comprehensively investigate PQ stems and leaves sourced from 7 different locations. Additionally, their bioactivities were evaluated against 5 fungi, 6 Gram-positive bacteria and 9 Gram-negative bacteria, a tumor cell line (A549), a non-tumor cell line (WI-26 VA4) and N2 wild-type Caenorhabditis elegans. RESULTS: Bioassay results demonstrated the efficacy of both leaves and stems against tumor cells, several bacteria and fungi, while only leaves exhibited anthelmintic activity against C. elegans. A total of 181 compounds were identified from PQ stems and leaves, including 43 ß-carbolines, 20 bis ß-carbolines, 8 canthinone alkaloids, 56 quassinoids, 12 triterpenoids, 13 terpenoid derivatives, 11 flavonoids, 7 coumarins, and 11 phenolic derivatives, from which 10 compounds were identified as indicator components for quality evaluation. Most alkaloids and triterpenoids were concentrated in PQ stems, while leaves exhibited higher levels of quassinoids and other carbohydrate (CHO) components. CONCLUSION: PQ leaves exhibit distinct chemical profiles and bioactivity with the stems, suggesting their suitability for medicinal purposes. So far, the antibacterial, antifungal, and anthelmintic activities of PQ leaves were first reported here, and considering PQ sustainability, the abundant leaves are recommended for increased utilization, particularly for their rich content of PQ quassinoids.
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Caenorhabditis elegans , Fitoquímicos , Picrasma , Hojas de la Planta , Tallos de la Planta , Hojas de la Planta/química , Picrasma/química , Animales , Tallos de la Planta/química , Caenorhabditis elegans/efectos de los fármacos , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Humanos , Línea Celular Tumoral , Estructura Molecular , Antineoplásicos Fitogénicos/farmacología , Alcaloides/farmacología , Cuassinas/farmacología , Cuassinas/química , Cuassinas/aislamiento & purificación , Antihelmínticos/farmacología , Antihelmínticos/química , Hongos/efectos de los fármacos , Flavonoides/farmacología , Flavonoides/análisisRESUMEN
The increasing accumulation of microplastics (MPs) in agroecosystems has raised significant environmental and public health concerns, facilitating the application of biodegradable plastics. However, the comparative effects of conventional and biodegradable MPs in agroecosystem are still far from fully understood. Here we developed microcosm experiments to reveal the ecological effects of conventional (polyethylene [PE] and polypropylene [PP]) and biodegradable (polyadipate/butylene terephthalate [PBAT] and polycaprolactone [PCL]) MPs (0, 1%, 5%; w/w) in the maize-soil ecosystem. We found that PCL MPs reduced plant production by 73.6-75.2%, while PE, PP and PBAT MPs elicited almost negligible change. The addition of PCL MPs decreased specific enzyme activities critical for soil nutrients cycling by 71.5-95.3%. Biodegradable MPs tended to reduce bacterial α-diversity. The 1% treatments of PE and PBAT, and PCL enhanced bacterial networks complexity, whereas 5% of PE and PBAT, and PP had adverse effect. Moreover, biodegradable MPs appeared to reduce the α-diversity and networks complexity of fungal community. Overall, PCL reduced the ecosystem multifunctionality, mainly by inhibiting the microbial metabolic activity. This study offers evidence that biodegradable MPs can impair agroecosystem multifunctionality, and highlights the potential risks to replace the conventional plastics by biodegradable ones in agricultural practices.
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Ecosistema , Microplásticos , Contaminantes del Suelo , Zea mays , Zea mays/metabolismo , Microplásticos/toxicidad , Contaminantes del Suelo/análisis , Biodegradación Ambiental , Poliésteres/metabolismo , Plásticos Biodegradables , Microbiología del Suelo , Hongos/metabolismo , Bacterias/metabolismo , Suelo/química , PolipropilenosRESUMEN
Terpenoid indole alkaloids (TIAs) are natural compounds found in medicinal plants that exhibit various therapeutic activities, such as antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, anti-helminthic, and anti-tumor properties. However, the production of these alkaloids in plants is limited, and there is a high demand for them due to the increasing incidence of cancer cases. To address this research gap, researchers have focused on optimizing culture media, eliciting metabolic pathways, overexpressing genes, and searching for potential sources of TIAs in organisms other than plants. The insufficient number of essential genes and enzymes in the biosynthesis pathway is the reason behind the limited production of TIAs. As the field of natural product discovery from biological species continues to grow, endophytes are being investigated more and more as potential sources of bioactive metabolites with a variety of chemical structures. Endophytes are microorganisms (fungi, bacteria, archaea, and actinomycetes), that exert a significant influence on the metabolic pathways of both the host plants and the endophytic cells. Bio-prospection of fungal endophytes has shown the discovery of novel, high-value bioactive compounds of commercial significance. The discovery of therapeutically significant secondary metabolites has been made easier by endophytic entities' abundant but understudied diversity. It has been observed that fungal endophytes have better intermediate processing ability due to cellular compartmentation. This paper focuses on fungal endophytes and their metabolic ability to produce complex TIAs, recent advancements in this area, and addressing the limitations and future perspectives related to TIA production.
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Endófitos , Hongos , Alcaloides de Triptamina Secologanina , Endófitos/metabolismo , Endófitos/genética , Hongos/metabolismo , Hongos/genética , Alcaloides de Triptamina Secologanina/metabolismo , Bacterias/metabolismo , Bacterias/genética , Bacterias/clasificación , Vías Biosintéticas , Plantas Medicinales/microbiología , Plantas Medicinales/metabolismo , Productos Biológicos/metabolismoRESUMEN
Epithelial cells orchestrate immune responses against fungal pathogens. This review highlights advances in integrating epithelial cells in immune responses against inhaled molds and dimorphic fungi, and against Candida species that colonize mucosal surfaces. In the lung, epithelial cells respond to interleukin-1 (IL-1) and interferon signaling to regulate effector cell influx and fungal killing. In the alimentary and vulvovaginal tracts, epithelial cells modulate fungal commensalism, invasive growth, and local immune tone, in part by responding to damage caused by candidalysin, a C. albicans peptide toxin, and through IL-17-dependent release of antimicrobial peptides that contribute to Candida colonization resistance. Understanding fungal-epithelial interactions in mammalian models of disease is critical to predict vulnerabilities and to identify opportunities for immune-based strategies to treat fungal infections.
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Células Epiteliales , Humanos , Células Epiteliales/microbiología , Células Epiteliales/inmunología , Animales , Candidiasis/inmunología , Candidiasis/microbiología , Hongos/inmunología , Hongos/fisiología , Hongos/patogenicidad , Candida/inmunología , Candida/fisiología , Interacciones Huésped-Patógeno/inmunología , Candida albicans/inmunología , Candida albicans/fisiología , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/inmunologíaRESUMEN
In this paper, three different Zn(II) complexes with (E)-2-(2-(1-(6-bromopyridin-2-yl)ethylidene)hydrazinyl)-N,N,N-trimethyl-2-oxoethan-1-aminium chloride (HLCl) have been synthesized and characterized by single crystal X-ray diffraction, elemental analysis, IR and NMR spectroscopy. All complexes are mononuclear, with the ligand (L) coordinated in a deprotonated formally neutral zwitterionic form via NNO donor set atoms. Complex 1 forms an octahedral geometry with the composition [ZnL2](BF4)2, while complexes 2 [ZnL(NCO)2] and 3 [ZnL(N3)2] form penta-coordinated geometry. Density functional theory (DFT) calculations were performed to enhance our understanding of the structures of the synthesized complexes and the cytotoxic activity of the complexes was tested against five human cancer cell lines (HeLa, A549, MDA-MB-231, K562, LS 174T) and normal human fibroblasts MRC-5. Additionally, antibacterial and antifungal activity of these complexes was tested against a panel of Gram-negative and Gram-positive bacteria, two fungal strains, and a yeast strain. It is noteworthy that all three complexes show selective antifungal activity comparable to that of amphotericin B. Molecular docking analysis predicted that geranylgeranyl pyrophosphate synthase, an enzyme essential for sterol biosynthesis, is the most likely target for inhibition by the tested complexes.
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Antibacterianos , Antifúngicos , Antineoplásicos , Complejos de Coordinación , Teoría Funcional de la Densidad , Hidrazonas , Pruebas de Sensibilidad Microbiana , Zinc , Humanos , Hidrazonas/química , Hidrazonas/farmacología , Hidrazonas/síntesis química , Zinc/química , Zinc/farmacología , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Estructura Molecular , Simulación del Acoplamiento Molecular , Ensayos de Selección de Medicamentos Antitumorales , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Modelos Moleculares , Hongos/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
CONTEXT: Allergic bronchopulmonary mycoses (ABPM) can be due to molds other than Aspergillus fumigatus in patients with cystic fibrosis (pwCF). We aimed to develop immunoassays for the detection of specific IgE (sIgE) directed against five fungal species involved in ABPM: Aspergillus terreus, Scedosporium apiospermum, Lomentospora prolificans, Rasamsonia argillacea, and Exophiala dermatitidis. MATERIALS AND METHODS: Serum samples (n = 356) from 238 pwCF, collected in eight CF care centers in France, Germany, and Italy, were analyzed by dissociated enhanced lanthanide fluorescent immunoassay (DELFIA®) to assess levels of sIgE directed against antigenic extracts of each fungus. Clinical, biological, and radiological data were collected for each episode. One hundred serum samples from healthy blood donors were used as controls. Sera were classified into four groups depending on the level of sIgE according to the quartile repartition calculated for the pwCF population. A score of 4 for values above the 3rd quartile corresponds to an elevated level of sIgE. RESULTS: PwCF showed higher levels of sIgE than controls. Based on criteria from the ABPA-ISHAM working group, with an additional criterion of "a sIgE score of 4 for at least one non-A. fumigatus mold", we were able to diagnose six cases of ABPM. CONCLUSIONS: Using 417 IU/mL as the threshold for total IgE and the same additional criterion, we identified seven additional pwCF with "putative ABPM". Detection of sIgE by DELFIA® showed good analytical performance and supports the role played by non-A. fumigatus molds in ABPM. However, commercially available kits usable in routine practice are needed to improve the diagnosis of ABPM.
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Anticuerpos Antifúngicos , Fibrosis Quística , Hongos , Inmunoglobulina E , Humanos , Fibrosis Quística/complicaciones , Inmunoglobulina E/sangre , Femenino , Masculino , Adulto , Adulto Joven , Adolescente , Hongos/inmunología , Hongos/clasificación , Hongos/aislamiento & purificación , Inmunoensayo/métodos , Niño , Anticuerpos Antifúngicos/sangre , Italia , Francia , Alemania , Preescolar , Persona de Mediana Edad , Aspergilosis Broncopulmonar Alérgica/diagnóstico , Aspergilosis Broncopulmonar Alérgica/inmunología , Aspergilosis Broncopulmonar Alérgica/sangreRESUMEN
Cadmium (Cd), a heavy metal, is negatively associated with plant growth. AMT (ammonium transporter) genes can confer Cd resistance and enhance nitrogen (N) uptake in soybeans. The potential of AMT genes to alleviate Cd toxicity by modulating rhizosphere microbiota remains unkonwn. Here, the rhizosphere microbial taxonomic and metabolic differences in three genotypes, i.e., double knockout and overexpression lines and wild type, were identified. The results showed that GmAMT2.1/2.2 genes could induce soybean to recruit beneficial microorganisms, such as Tumebacillus, Alicyclobacillus, and Penicillium, by altering metabolites. The bacterial, fungal, and cross-kingdom synthetic microbial communities (SynComs) formed by these microorganisms can help soybean resist Cd toxicity. The mechanisms by which SynComs help soybeans resist Cd stress include reducing Cd content, increasing ammonium (NH4+-N) uptake and regulating specific functional genes in soybeans. Overall, this study provides valuable insights for the developing microbial formulations that enhance Cd resistance in sustainable agriculture.
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Compuestos de Amonio , Cadmio , Glycine max , Microbiota , Nitrógeno , Rizosfera , Microbiología del Suelo , Cadmio/metabolismo , Cadmio/toxicidad , Glycine max/microbiología , Compuestos de Amonio/metabolismo , Nitrógeno/metabolismo , Microbiota/efectos de los fármacos , Bacterias/genética , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Hongos/genética , Hongos/metabolismo , Hongos/efectos de los fármacos , Raíces de Plantas/microbiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Environmental microorganisms commonly inhabit dense multispecies biofilms, fostering mutualistic relationships and co-evolution. However, the mechanisms underlying biofilm formation and microbial interactions within the Baijiu fermentation microecosystem remain poorly understood. Hence, the objective of this study was to investigate the composition, structure, and interactions of microorganisms residing in biofilms on environmental surfaces in Baijiu production. The results revealed a shift in the bacteria-fungi interaction network following fermentation, transitioning from a cooperative/symbiotic relationship to a competitive/antagonistic dynamic. Core microbiota within the biofilms comprised lactic acid bacteria (LAB), yeast, and filamentous fungi. From the environmental surface samples, we isolated two strains of LAB (Lactiplantibacillus pentosus EB27 and Pediococcus pentosaceus EB35) and one strain of yeast (Pichia kudriavzevii EF8), all displaying remarkable biofilm formation and fermentation potential. Co-culturing LAB and yeast demonstrated a superior capacity for dual-species biofilm formation compared to mono-species biofilms. The dual-species biofilm displayed a two-layer structure, with LAB in the lower layer and serving as the foundation for the yeast community in the upper layer. The upper layer exhibited a dense distribution of yeast, enhancing aerobic respiration. Metabolic activities in the dual-species biofilm, such as ABC transporter, oxidative phosphorylation, citric acid cycle, sulfur metabolism, glycine, serine, threonine metabolism, lysine degradation, and cysteine and methionine metabolism, showed significant alterations compared to LAB mono-species biofilms. Moreover, bacterial chemotaxis, starch, and sucrose metabolism in the dual-species biofilm exhibited distinct patterns from those observed in the yeast mono-species biofilm. This study demonstrated that a core microbiota with fermentation potential may exist in the form of a biofilm on the surface of a Baijiu brewing environment. These findings provide a novel strategy for employing synthetic stable microbiotas in the intelligent brewing of Baijiu.
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Biopelículas , Fermentación , Interacciones Microbianas , Biopelículas/crecimiento & desarrollo , Interacciones Microbianas/fisiología , Microbiología de Alimentos , Cerveza/microbiología , Microbiota/fisiología , Técnicas de Cocultivo , Lactobacillales/metabolismo , Lactobacillales/fisiología , Hongos/metabolismo , Hongos/fisiología , Pediococcus pentosaceus/metabolismoRESUMEN
Mycoplasma genitalium is a sexually transmitted bacterium associated with urogenital disease syndromes in the US and worldwide. The global rise in drug resistance in M. genitalium necessitates the development of novel drugs to treat this pathogen. To address this need, we have screened extracts from a library of fungal isolates assembled through the University of Oklahoma Citizen Science Soil Collection Program. Analysis of one of the bioactive extracts using bioassay-guided fractionation led to the purification of the compound PF1140 (1) along with a new and several other known pyridones. The N-hydroxy pyridones are generally regarded as siderophores with high binding affinity for iron(III) under physiological conditions. Results from UV-vis absorption spectroscopy-based titration experiments revealed that 1 complexes with Fe3+. As M. genitalium does not utilize iron, we propose that the PF1140-iron complex induces cytotoxicity by facilitating the cellular uptake of iron, which reacts with endogenous hydrogen peroxide to produce toxic hydroxyl radicals.