RESUMEN
Fusarium ear rot (FER), caused by the fungal pathogen Fusarium verticillioides, stands as one of the most economically burdensome and pervasive diseases affecting maize worldwide. Its impact on food security is particularly pronounced due to the production of fumonisins, toxic secondary metabolites that pose serious health risks, especially for livestock. FER disease severity is complex and polygenic, with few resistance (R) genes being identified for use in breeding resistant varieties. While FER is the subject of several breeding programs, only a few studies have investigated entire populations of F. verticillioides with corresponding virulence data to better understand and characterize the pathogenomics. Here, we sequenced and compared the genomes of 50 Fusarium isolates (43 F. verticillioides and 7 other Fusarium spp.) that were used to inoculate a diverse maize population. Our objectives were to elucidate the genome size and composition of F. verticillioides, explore the variable relationship between fumonisin production and visual disease severity, and shed light on the phylogenetic relationships among the isolates. Additionally, we conducted a comparative analysis of the nucleotide variants (SNPs) and the isolates' effectoromes to uncover potential genetic determinants of pathogenicity. Our findings revealed several promising leads, notably the association of certain gene groups, such as pectate lyase, with disease severity. These genes should be investigated further as putative alleles for breeding resistant maize varieties. We suggest that, beyond validation of the alleles identified in this study, researchers validate each phenotypic dataset on an individual basis, particularly if considering fumonisin concentrations and when using diverse populations. Our study underscores the importance of genomic analysis in tackling FER and offers insights that could inform the development of resilient maize cultivars. By leveraging advances in genomics and incorporating pathogen populations into breeding programs, resistance to FER can be advanced.
Asunto(s)
Fusarium , Genómica , Enfermedades de las Plantas , Zea mays , Fusarium/genética , Fusarium/patogenicidad , Zea mays/microbiología , Zea mays/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Genómica/métodos , Genoma Fúngico , Filogenia , Fumonisinas/metabolismo , Polimorfismo de Nucleótido Simple , Resistencia a la Enfermedad/genéticaRESUMEN
Fumonisin B1 (FB1) targets sphingolipid biosynthesis, inhibiting ceramide synthases. In this issue of Structure, Zhang et al.1 determined the cryoelectron microscopic structures of yeast ceramide synthase in complex with FB1 and its acylated derivative, acyl-FB1, revealing a two-step "ping-pong" mechanism for the N-acylation of FB1 and how it inhibits ceramide synthase.
Asunto(s)
Microscopía por Crioelectrón , Fumonisinas , Oxidorreductasas , Fumonisinas/química , Fumonisinas/metabolismo , Oxidorreductasas/metabolismo , Oxidorreductasas/química , Oxidorreductasas/antagonistas & inhibidores , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/metabolismo , Acilación , Modelos Moleculares , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/antagonistas & inhibidores , Esfingolípidos/metabolismo , Esfingolípidos/químicaRESUMEN
Rice plays an important role in the daily diet in China and therefore its quality and safety have been of great concern. However, few systematic studies have investigated Fusarium community and toxins in rice grains. Here, we collected 1381 rice samples from Jiangsu Province in eastern China and found a higher frequency of zearalenone (ZEN), deoxynivalenol (DON), fumonisins (FBs), and beauvericin (BEA). The positive samples were individually contaminated with a minimum of one and a maximum of ten toxins. Fusarium was isolated and identified as the major fungus, which exhibited temporal and geographical distribution. The most prevalent species complexes within this genus were Fusarium incarnatum-equiseti species complex (FIESC), Fusarium fujikuroi species complex (FFSC), and Fusarium sambucinum species complex (FSAMSC). Nevertheless, the amplicon sequence analysis revealed a low relative abundance of Fusarium in the rice panicles, and the fungal community exhibited an irregular change along with the symptom's emergence. In vitro toxigenic profiles of Fusarium strains showed significant complexity and specificity depending on the type and content. FIESC strains were non-pathogenic to wheat heads and weakly pathogenic to maize ears, respectively, accumulating lower amounts of toxins than F. asiaticum and F. fujikuroi. There was no significant variation in the ability to cause panicle blight in rice among the various species tested. Our study provides detailed information about the contamination of Fusarium toxins and community in rice after harvest. This information is valuable for understanding the relationship between Fusarium and rice and for developing effective control strategies.
Asunto(s)
Contaminación de Alimentos , Fusarium , Micotoxinas , Oryza , Fusarium/aislamiento & purificación , Fusarium/genética , Oryza/microbiología , Contaminación de Alimentos/análisis , Micotoxinas/análisis , China , Depsipéptidos/análisis , Tricotecenos/análisis , Microbiología de Alimentos , Zearalenona/análisis , Fumonisinas/análisisRESUMEN
Maize, one of the most important cereal crops in Bangladesh, is severely contaminated by fumonisin, a carcinogenic secondary metabolite produced by Fusarium including Fusarium proliferatum. Biocontrol with Bacillus strains is an effective approach to controlling this F. proliferatum as Bacillus has proven antagonistic properties against this fungus. Therefore, the present study aimed to determine how native Bacillus strains can reduce fumonisin in maize cultivated in Bangladesh, where BDISO76MR (Bacillus subtilis) strains showed the highest efficacy both in vitro in detached cob and in planta under field conditions. The BDISO76MR strain could reduce the fumonisin concentration in detached cob at 98.52% over untreated control, by inhibiting the conidia germination and spore formation of F. proliferatum at 61.56% and 77.01%, respectively in vitro. On the other hand, seed treatment with formulated BDISO76MR showed higher efficacy with a reduction of 97.27% fumonisin contamination compared to the in planta cob inoculation (95.45%) over untreated control. This implies that Bacillus-based formulation might be a potential approach in mitigating fumonisin contamination in maize to ensure safe food and feed.
Asunto(s)
Bacillus subtilis , Contaminación de Alimentos , Fumonisinas , Fusarium , Semillas , Zea mays , Zea mays/microbiología , Fumonisinas/metabolismo , Fusarium/metabolismo , Semillas/microbiología , Contaminación de Alimentos/prevención & control , Contaminación de Alimentos/análisis , RizosferaRESUMEN
Maize (Zea mays L.) may be infected by Fusarium verticillioides and F. proliferatum, and consequently contaminated with fumonisins (FBs), as well as the co-products of bioethanol intended for animal feed. Laccase enzymes have a wide industrial application such as mycotoxin degradation. The aims were to isolate and identify fungal laccase-producing strains, to evaluate laccase production, to determine the enzymatic stability under fermentation conditions, and to analyse the effectiveness in vitro of enzymatic extracts (EEs) containing laccases in degrading FB1. Strains belonging to Funalia trogii, Phellinus tuberculosus, Pleurotus ostreatus, Pycnoporus sanguineus and Trametes gallica species showed laccase activity. Different isoforms of laccases were detected depending on the evaluated species. For the FB1 decontamination assays, four enzymatic activities (5, 10, 15 and 20 U/mL) were tested, in the absence and presence of vanillic acid (VA) and 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) as redox mediators (1 and 10 mM). Trametes gallica B4-IMICO-RC EE was the most effective strain in buffer, achieving a 60% of FB1 reduction. Laccases included in EEs remained stable at different alcoholic degrees in maize steep liquor (MSL), but no significant FB1 reduction was observed under the conditions evaluated using MSL. This study demonstrate that although laccases could be good candidates for the development of a strategy to reduce FB1, further studies are necessary to optimise this process in MSL.
Asunto(s)
Fumonisinas , Lacasa , Zea mays , Zea mays/microbiología , Zea mays/química , Lacasa/metabolismo , Fumonisinas/metabolismo , Etanol/metabolismo , Fusarium/enzimología , Fusarium/metabolismo , Descontaminación/métodos , Fermentación , Hongos/enzimología , BiocombustiblesRESUMEN
Fumonisin B1 (FB1), a mycotoxin produced by Fusarium species, is prevalent in crops and animal feed, posing significant health risks to livestock and humans. FB1 induces oxidative stress in Sertoli cells, destroys testicular structure, and affects spermatogenesis. However, methods to mitigate the reproductive toxicity of FB1 in testes remain unknown. Quercetin, a natural flavonoid antioxidant, may offer protective benefits. This study investigated the protective effects and mechanisms of quercetin against FB1-induced reproductive toxicity in TM4 cells (a Sertoli cell line). The results indicated that 40 µM quercetin improved cell viability, reduced apoptosis, and preserved cell functions. Quercetin also decreased reactive oxygen species (ROS) levels in TM4 cells exposed to FB1, enhanced the expression of antioxidant genes, and improved mitochondrial membrane potential. Compared with FB1 alone, the combination of quercetin and FB1 increased ATP levels, as well as pyruvate and lactic acid, the key glycolysis products. Furthermore, this combination elevated the mRNA and protein expression of glycolysis-related genes, including glucose-6-phosphate isomerase 1 (Gpi1), hexokinase 2 (Hk2), aldolase (Aldoa), pyruvate kinase, muscle (Pkm), lactate dehydrogenase A (Ldha) and phosphofructokinase, liver, B-type (Pfkl). Quercetin also boosted the activity of PKM and LDHA, two crucial glycolytic enzymes. In summary, quercetin mitigates FB1-induced toxicity in TM4 cells by reducing ROS levels and enhancing glycolysis. This study offers new insights into preventing and treating FB1-induced toxic damage to the male reproductive system and highlights the potential application of quercetin.
Asunto(s)
Supervivencia Celular , Fumonisinas , Quercetina , Especies Reactivas de Oxígeno , Células de Sertoli , Quercetina/farmacología , Fumonisinas/toxicidad , Masculino , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Animales , Supervivencia Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Ratones , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Glucólisis/efectos de los fármacos , Sustancias Protectoras/farmacologíaRESUMEN
Rabbit bucks (bodyweight 5 kg) underwent dietary intoxication with fumonisin B series mycotoxins (FB1 + FB2 + FB3, 15 mg/kg diet) for 14 days to test the applicability of positron emission tomography-magnetic resonance (PET MR) hybrid imaging in characterizing experimentally induced mild hepatotoxicosis. 18F-fluorodeoxyglucose (18F-FDG) radiotracer-aided imaging was performed before and after FBs administration on identical animals, and at both time points, blood was sampled for haematology and clinical chemistry. Kinetic PET image analysis revealed time-activity curves with uptake maxima below 1 min in the liver, renal cortex, portal vein, lung and coarctatio aortae. In the frame of static PET image analysis, based on the standardized uptake value (SUV), the so-called metabolic liver volume (MLV, liver volume defined by over 0.9 × average liver SUV) and the total liver glycolysis (TLG, MLV multiplied by the SUVmean) were calculated. Mycotoxicosis increased total liver glycolysis (p < 0.04) after 14 days and liver tissue TLG inhomogeneity was minimal. Pearson correlation between TLG and alkaline phosphatase (ALP) was positive (0.515), while negative with LDH and AST (- 0.721 and - 0.491, respectively). Results indicate a slight hepatic mycotoxin effect and significantly increased glucose uptake intensity, which has been sensitively detected with molecular imaging (18F-FDG PET MRI) in the rabbit model.
Asunto(s)
Fluorodesoxiglucosa F18 , Fumonisinas , Hígado , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Animales , Conejos , Fumonisinas/toxicidad , Hígado/metabolismo , Hígado/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones/métodos , Glucosa/metabolismo , MasculinoRESUMEN
Fumonisin B1 (FB1) is a mycotoxin affecting animal health through the food chain and has been closely associated with several diseases such as pulmonary edema in pigs and diarrhea in poultry. FB1 is mainly metabolized in the liver. Although a few studies have shown that FB1 causes liver damage, the molecular mechanism of liver damage is unclear. This study aimed to evaluate the role of liver damage, nuclear xenobiotic receptor (NXR) response and cytochrome P450 (CYP450)-mediated defense response during FB1 exposure. A total of 120 young quails were equally divided into two groups (control and FB1 groups). The quails in the control group were fed on a normal diet, while those in the FB1 group were fed on a quail diet containing 30 mg/kg for 42 days. Histopathological and ultrastructural changes in the liver, biochemical parameters, inflammatory factors, endoplasmic reticulum (ER) factors, NXR response and CYP450 cluster system and other related genes were examined at 14 days, 28 days and 42 days. The results showed that FB1 exposure impaired the metabolic function and caused liver injury. FB1 caused ER stress and decreased adenosine triphosphatease activity, induced the expression of inflammation-related genes such as interleukin 6 and nuclear factor kappa-B, and promoted inflammation. In addition, FB1 disrupted the expression of multiple CYP450 isoforms by activating nuclear xenobiotic receptors (NXRs). The present study confirms that FB1 exposure disturbs the homeostasis of cytochrome P450 systems (CYP450s) in quail liver by activating NXR responses and thereby causing liver damage. This study's findings provide insight into the molecular mechanisms of FB1-induced hepatotoxicity.
Asunto(s)
Sistema Enzimático del Citocromo P-450 , Retículo Endoplásmico , Fumonisinas , Inflamación , Hígado , Animales , Fumonisinas/toxicidad , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Inflamación/inducido químicamente , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Codorniz , Estrés del Retículo Endoplásmico/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Enfermedad Hepática Inducida por Sustancias y DrogasRESUMEN
Maize (Zea mays L.) is an important cereal crop worldwide. Contaminated maize kernels pose a significant mycotoxin exposure risk for humans in Latin America. Fumonisins, the most prevalent mycotoxin in maize, typically occur during pre-harvest conditions leading to significant economic losses. Various factors, including weather conditions, may influence this contamination. This study aimed to determine the association between fumonisin B1 (FB1) contamination, prevalence of Fusarium verticillioides, weather conditions and kernel quality in the two primary maize production areas in Costa Rica (Brunca and Chorotega). All maize samples (100%) showed FB1 contamination, with higher concentrations in samples from Brunca region, consistent with the presence of F. verticilliodes. Weather conditions appeared to play an important role in this contamination, since Brunca region had the highest mean temperature and relative humidity after maize silking (R1) and the total monthly rainfall in this region was significantly higher during the last two months of maize cultivation (grain-filling and physiological maturity stages R3 to R6). Interestingly, this study found a negative correlation between grain damage and kernel contamination with FB1 and F. verticillioides. The concentration of mineral nutrients in kernels from both regions was largely similar. Most nutrients in kernels exhibited a negative correlation with FB1, particularly nitrogen. Zinc and phosphorus were the only nutrients in kernels showing a positive correlation with FB1 in samples from the Brunca region. The results highlight elevated levels of FB1 contamination in maize and contribute to a better understanding of pre-harvest factors influencing FB1 contamination in tropical conditions.
Asunto(s)
Fumonisinas , Fusarium , Zea mays , Fumonisinas/análisis , Zea mays/microbiología , Zea mays/química , Costa Rica , Contaminación de Alimentos/análisis , Tiempo (Meteorología)RESUMEN
This study aimed to determine whether oral fumonisin exposure contributes to the development of psoriasis. Oral administration of fumonisin B1 (FB1, 0.1 mg/kg) or fumonisin B2 (FB2, 0.1 mg/kg) was conducted for 10 days, in addition to the induction of psoriatic symptoms through topical application of 5% imiquimod cream from day 6 to day 10 (5 days) in female BALB/c mice. The results demonstrated that oral administration of FB2 significantly exacerbated psoriatic symptoms, including skin thickness, itching behavior, transepidermal water loss, immune cell infiltration in the dermis, and proinflammatory cytokine production. However, no changes were observed following exposure to FB1. Our results confirm that oral exposure to FB2 adversely affects the pathogenesis of psoriasis by increasing skin thickness and impairing barrier function.
Asunto(s)
Fumonisinas , Imiquimod , Ratones Endogámicos BALB C , Psoriasis , Animales , Psoriasis/inducido químicamente , Psoriasis/patología , Psoriasis/metabolismo , Imiquimod/efectos adversos , Fumonisinas/toxicidad , Ratones , Femenino , Administración Oral , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Citocinas/metabolismo , Modelos Animales de EnfermedadRESUMEN
Mycotoxins are secondary products produced primarily by fungi and are pathogens of animals and cereals, not only affecting agriculture and the food industry but also causing great economic losses. The development of rapid and sensitive methods for the detection of mycotoxins in food is of great significance for livelihood issues. This study employed an amino-functionalized zirconium luminescent metal-organic framework (LOF) (i.e., UiO-66-NH2). Click chemistry was utilized to assemble UiO-66-NH2 in a controlled manner, generating LOF assemblies to serve as probes for fluorescence-linked immunoassays. The proposed fluoroimmunoassay method for Zearalenone (ZEN) and Fumonisin B1 (FB1) detection based on the UiO-66-NH2 assembled probe (CLICK-FLISA) afforded a linear response range of 1-20 µmol/L for ZEN, 20 µmol/L for FB1, and a very low detection limit (0.048-0.065 µmol/L for ZEN; 0.048-0.065 µmol/L for FB1). These satisfying results demonstrate promising applications for on-site quick testing in practical sample analysis. Moreover, the amino functionalization may also serve as a modification strategy to design luminescent sensors for other food contaminants.
Asunto(s)
Fumonisinas , Estructuras Metalorgánicas , Zea mays , Zearalenona , Fumonisinas/análisis , Zearalenona/análisis , Estructuras Metalorgánicas/química , Zea mays/química , Química Clic , Fluoroinmunoensayo/métodos , Técnicas Biosensibles , Contaminación de Alimentos/análisis , Límite de Detección , Micotoxinas/análisisRESUMEN
Mycotoxins, especially aflatoxin B1 (AFB1) and fumonisin B1 (FMB1), are common contaminants in cereal-based foods. Instances of contamination are predicted to increase due to the current challenges induced by climate change. Despite the health benefits of whole grains, the presence of mycotoxins in bran remains a concern. Nonetheless, previous research indicates that wheat bran can adsorb mutagens. Therefore, this study investigated the capacity of maize, wheat, and oat brans to adsorb AFB1 and FMB1 under varying in vitro conditions, including pH, binding time, temperature, particle size, and the amount of bran utilized. Maize bran demonstrated a high AFB1 adsorption capacity (>78%) compared to wheat and oat brans. However, FMB1 was not adsorbed by the brans, possibly due to its hydrophilic nature. Lower temperature (≤25 °C) enhanced AFB1 adsorption efficacy in wheat and oat bran, while for maize bran, the highest adsorption occurred at 37 °C. A linear model following Henry's law best explained AFB1 adsorption by the brans. Further studies identified the pericarp layer of bran as the primary site of AFB1 adsorption, with the initial liquid volume being a critical factor. The study concludes that bran could potentially act as an effective bioadsorbent. Further research is essential to confirm the adsorption efficacy and the bioavailability of AFB1 through in vivo experiments.
Asunto(s)
Aflatoxina B1 , Avena , Fibras de la Dieta , Contaminación de Alimentos , Fumonisinas , Triticum , Zea mays , Zea mays/química , Fumonisinas/química , Triticum/química , Adsorción , Aflatoxina B1/química , Avena/química , Contaminación de Alimentos/prevención & control , Contaminación de Alimentos/análisis , Temperatura , Concentración de Iones de HidrógenoRESUMEN
Although the cell membrane and cytoskeleton play essential roles in cellular morphogenesis, the interaction between the membrane and cytoskeleton is poorly understood. Cotton fibers are extremely elongated single cells, which makes them an ideal model for studying cell development. Here, we used the sphingolipid biosynthesis inhibitor, fumonisin B1 (FB1), and found that it effectively suppressed the myeloblastosis (MYB) transcription factor GhMYB86, thereby negatively affecting fiber elongation. A direct target of GhMYB86 is GhTUB7, which encodes the tubulin protein, the major component of the microtubule cytoskeleton. Interestingly, both the overexpression of GhMYB86 and GhTUB7 caused an ectopic microtubule arrangement at the fiber tips, and then leading to shortened fibers. Moreover, we found that GhMBE2 interacted with GhMYB86 and that FB1 and reactive oxygen species induced its transport into the nucleus, thereby enhancing the promotion of GhTUB7 by GhMYB86. Overall, we established a GhMBE2-GhMYB86-GhTUB7 regulation module for fiber elongation and revealed that membrane sphingolipids affect fiber elongation by altering microtubule arrangement.
Asunto(s)
Gossypium , Microtúbulos , Proteínas de Plantas , Esfingolípidos , Microtúbulos/metabolismo , Gossypium/genética , Gossypium/metabolismo , Esfingolípidos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las Plantas , Fumonisinas/farmacología , Fibra de Algodón , Especies Reactivas de Oxígeno/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genéticaRESUMEN
Maize grain samples collected from 129 small-scale farmers' stores in southern and southwestern Ethiopia were analysed by LC-MS/MS for a total of 218 mycotoxins and other fungal metabolites of which 15% were regulated mycotoxins. Mycotoxins produced by Penicillium, Aspergillus, and Fusarium accounted for 31%, 17%, and 12% of the metabolites, respectively. Most of the current samples were contaminated by masked and/or emerging mycotoxins with moniliformin being the most prevalent one, contaminating 93% of the samples. Each sample was co-contaminated by 3 to 114 mycotoxins/fungal metabolites. Zearalenone, fumonisin B1, and deoxynivalenol were the dominant mycotoxins, occurring in 78%, 61%, and 55% of the samples with mean concentrations of 243, 429, and 530 µg/kg, respectively. The widespread co-occurrence of several mycotoxins in the samples may pose serious health risks due to synergistic/additional effects.
Asunto(s)
Contaminación de Alimentos , Fumonisinas , Micotoxinas , Espectrometría de Masas en Tándem , Zea mays , Zea mays/química , Zea mays/microbiología , Etiopía , Micotoxinas/análisis , Contaminación de Alimentos/análisis , Fumonisinas/análisis , Humanos , Zearalenona/análisis , Fusarium/química , Fusarium/metabolismo , Tricotecenos/análisis , Penicillium , Aspergillus , Almacenamiento de Alimentos , Cromatografía Liquida/métodos , CiclobutanosRESUMEN
The electrochemical detection of biosensors is largely governed by the changes in physical properties of redox probes, which are susceptible to electrode substrate effects, inhibiting sensor sensitivity. In this work, a light-driven electrochemical biosensor based on a hybrid nanoantenna was developed for the sensitive detection of fumonisin B1 (FB1). The hybrid nanoantenna sensing interface was constructed by coupling CdSe quantum dots (QDs)-DNA nanowire and graphdiyne oxide composites loaded with methylene blue and gold nanorods (GDYO-MB-Au NRs) using a tetrahedral DNA nanostructure, which acted as a light-driven unit and an amplification unit, respectively. The hybrid nanoantenna with light-driven properties facilitated the alteration in the chemical properties of MB at the sensing interface; that is, MB was degraded under light illumination. The stripping of the CdSe QDs-DNA nanowire triggered by the binding of FB1 could degrade the light-driven capability, thereby improving the electrochemical signal through depressing MB degradation. Taking advantage of the photodegradation of MB by the hybrid nanoantenna, the developed biosensor reduced the background signal and increased the detection sensitivity. The developed biosensor exhibited a linear detection range from 0.5 fg mL-1 to 10 pg mL-1 and a detection limit down to 0.45 fg mL-1. This strategy shows great promise for the fabrication of highly sensitive electrochemical biosensors.
Asunto(s)
Técnicas Biosensibles , ADN , Técnicas Electroquímicas , Fumonisinas , Puntos Cuánticos , Fumonisinas/análisis , ADN/química , Puntos Cuánticos/química , Luz , Compuestos de Cadmio/química , Oro/química , Compuestos de Selenio/química , Nanotubos/química , Límite de Detección , Nanocables/químicaRESUMEN
Ceramide synthases (CerSs) play crucial roles in sphingolipid metabolism and have emerged as promising drug targets for metabolic diseases, cancers, and antifungal therapy. However, the therapeutic targeting of CerSs has been hindered by a limited understanding of their inhibition mechanisms by small molecules. Fumonisin B1 (FB1) has been extensively studied as a potent inhibitor of eukaryotic CerSs. In this study, we characterize the inhibition mechanism of FB1 on yeast CerS (yCerS) and determine the structures of both FB1-bound and N-acyl-FB1-bound yCerS. Through our structural analysis and the observation of N-acylation of FB1 by yCerS, we propose a potential ping-pong catalytic mechanism for FB1 N-acylation by yCerS. Lastly, we demonstrate that FB1 exhibits lower binding affinity for yCerS compared to the C26- coenzyme A (CoA) substrate, suggesting that the potent inhibitory effect of FB1 on yCerS may primarily result from the N-acyl-FB1 catalyzed by yCerS, rather than through direct binding of FB1.
Asunto(s)
Fumonisinas , Oxidorreductasas , Unión Proteica , Saccharomyces cerevisiae , Fumonisinas/metabolismo , Fumonisinas/química , Oxidorreductasas/metabolismo , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/química , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimología , Acilación , Modelos Moleculares , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Cristalografía por Rayos X , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/antagonistas & inhibidores , Dominio Catalítico , Sitios de Unión , Coenzima A/metabolismo , Coenzima A/química , Especificidad por SustratoRESUMEN
This study explores the implementation of the One Sample Strategy (OSS), a co-regulation program aimed at managing mycotoxin risk in Texas maize. Fumonisin-contaminated cereals and oilseeds that contain greater than 5 mg kg-1 of the toxin (B1, B2, and B3) are a risk for equids and rabbits, and levels greater than 60 mg kg-1 are a risk to ruminants. The OSS, previously successful in managing aflatoxin risk in Texas maize, was evaluated for its effectiveness in handling fumonisin risk in maize, specifically as it relates to ruminants. In 2017, 25 analysts across seven firms qualified to participate in the program. To ensure greater accuracy in testing, working control samples were provided to the participating OSS firms with the requirement that their results fall within +/- 20% of the target concentration. Ninety-four percent of the working controls met this specification. The capability to grind maize to the OSS prescribed particle size was met by 100% of participants. To verify testing accuracy, file samples collected from each OSS firm were analysed by UPLC-MS/MS. The 177 fumonisin verification samples analysed by Office of the Texas State Chemist (OTSC) were correlated (r = 0.93) with co-regulation laboratories. Results were plotted in an operating curve to depict type I and type II errors. Error analysis revealed a type I error rate of 13% and type II error rate of 2% for the 5 mg kg-1 guidance level, and 6% and 8%, respectively, for the 60 mg kg-1 guidance level. For 2017, 994 official reports of analysis for fumonisin in whole maize in the Texas High Plains were issued by the seven laboratories that employed 25 OTSC-credentialed analysts. The OSS co-regulation program, supported by a quality systems approach and government regulations, has proven effective in managing fumonisin risk in Texas maize, enhancing both market confidence and livestock safety.
Asunto(s)
Contaminación de Alimentos , Fumonisinas , Zea mays , Zea mays/química , Fumonisinas/análisis , Contaminación de Alimentos/análisis , Texas , Espectrometría de Masas en Tándem , Animales , Medición de Riesgo , Inocuidad de los Alimentos , HumanosRESUMEN
Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely found as cereal contaminants, and their co-consumption is associated with liver cancer. Both are immunotoxic, but their interactions have been little studied. This work was aimed to evaluate in mouse spleen mononuclear cells (SMC) the effects of the exposure to AFB1 (5-50 µM), FB1 (25-250 µM), and AFB1-FB1 mixtures (MIX) on the in vitro differentiation of regulatory T cells (Treg and Tr1-like) and Th17 cells, as well as elucidate the contribution of aryl hydrocarbon receptor (Ahr) in such effects. AFB1 and mainly MIX induced cytotoxicity in activated CD4 cells via Ahr signaling. AFB1 (5 µM) increased the Treg cell differentiation, but its combination with FB1 (25 µM) also reduced Th17 cell expansion by Ahr-dependent mechanisms. Therefore, this mixture could enhance the Treg/Th17 cell ratio and favor immunosuppression and escape from tumor immunosurveillance to a greater extent than individual mycotoxins. Whereas, AFB1-FB1 mixtures at medium-high doses inhibited the Tr1-like cell expansion induced by the individual mycotoxins and affected Treg and Th17 cell differentiation in Ahr-independent and dependent manners, respectively, which could alter anti-inflammatory and Th17 immune responses. Moreover, individual FB1 altered regulatory T and Th17 cell development independently of Ahr. In conclusion, AFB1 and FB1 interact by modifying Ahr signaling, which is involved in the immunotoxicity as well as in the alteration of the differentiation of Treg, Tr1-like, and Th17 cells induced by AFB1-FB1 mixtures. Therefore, Ahr is implicated in the regulation of the anti- and pro-inflammatory responses caused by the combination of AFB1 and FB1.
Asunto(s)
Aflatoxina B1 , Diferenciación Celular , Fumonisinas , Receptores de Hidrocarburo de Aril , Linfocitos T Reguladores , Células Th17 , Receptores de Hidrocarburo de Aril/metabolismo , Aflatoxina B1/toxicidad , Animales , Células Th17/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacos , Fumonisinas/toxicidad , Ratones , Diferenciación Celular/efectos de los fármacosRESUMEN
Fumonisin B1 (FB1) is a mycotoxin, a water-soluble metabolite produced by Fusarium cepacia, which mainly contaminates grain and its products and is acutely toxic and potentially carcinogenic to certain domestic animals. In this work, plasma nanocomposites of Fe3O4@Cu@Cu2O with magnetic and optoelectronic properties were synthesized as a sensing platform. On one hand, the surface plasmon resonance (SPR) of metallic Cu accelerates the electron transfer rate. On the other hand, plasma-induced resonance energy transfer of metals and semiconductors can improve the utilization efficiency of light energy. A split photoelectrochemical (PEC) sensor based on Fe3O4@Cu@Cu2O was proposed for the detection of FB1. The sensor has a wide linear range of 1.0-10 000 pg mL-1 and a low detection limit of 0.28 pg mL-1 (LOD, S/N = 3), which can realize the specific detection of FB1 in real samples.
Asunto(s)
Cobre , Técnicas Electroquímicas , Fumonisinas , Límite de Detección , Fumonisinas/química , Fumonisinas/análisis , Cobre/química , Técnicas Electroquímicas/métodos , Nanocompuestos/química , Resonancia por Plasmón de Superficie/métodos , Procesos FotoquímicosRESUMEN
Fusarium verticillioides produces fumonisins, which are mycotoxins inhibiting sphingolipid biosynthesis in humans, animals, and other eukaryotes. Fumonisins are presumed virulence factors of plant pathogens, but may also play a role in interactions between competing fungi. We observed higher resistance to added fumonisin B1 (FB1) in fumonisin-producing Fusarium verticillioides than in nonproducing F. graminearum, and likewise between isolates of Aspergillus and Alternaria differing in production of sphinganine-analog toxins. It has been reported that in F. verticillioides, ceramide synthase encoded in the fumonisin biosynthetic gene cluster is responsible for self-resistance. We reinvestigated the role of FUM17 and FUM18 by generating a double mutant strain in a fum1 background. Nearly unchanged resistance to added FB1 was observed compared to the parental fum1 strain. A recently developed fumonisin-sensitive baker's yeast strain allowed for the testing of candidate ceramide synthases by heterologous expression. The overexpression of the yeast LAC1 gene, but not LAG1, increased fumonisin resistance. High-level resistance was conferred by FUM18, but not by FUM17. Likewise, strong resistance to FB1 was caused by overexpression of the presumed F. verticillioides "housekeeping" ceramide synthases CER1, CER2, and CER3, located outside the fumonisin cluster, indicating that F. verticillioides possesses a redundant set of insensitive targets as a self-resistance mechanism.