Chemical strategies for triggering the immune response to the mycotoxin patulin.
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ABSTRACT:
SUBMITTER: Duncan H
PROVIDER: S-EPMC8648828 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Patulin, an emerging mycotoxin with high toxicity, poses great risks to public health. Considering the poor antibody production in patulin immunization, this study focuses on the four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics to reveal the immune response of patulin in rabbits. The rabbit immunization was performed with the complete developed antigens of patulin, followed by the identification of the immune serum. A total of 554 differential proteins, including 292 up-regulated proteins and 262 down-regulated proteins, were screened; the differential proteins were annotated; and functional enrichment analysis was performed. The differential proteins were associated with the pathways of metabolism, gene information processing, environmental information processing, cellular processes, and organismal systems. The functional enrichment analysis indicated that the immunization procedures mostly resulted in the regulation of biochemical metabolic and signal transduction pathways, including the biosynthesis of amino acid (glycine, serine, and threonine), ascorbate, and aldarate metabolism; fatty acid degradation; and antigen processing and presentation. The 14 key proteins with high connectivity included G1U9T1, B6V9S9, G1SCN8, G1TMS5, G1U9U0, A0A0G2JH20, G1SR03, A0A5F9DAT4, G1SSA2, G1SZ14, G1T670, P30947, P29694, and A0A5F9C804, which were obtained by the analysis of protein-protein interaction networks. This study could provide potential directions for protein interaction and antibody production for food hazards in animal immunization.
| S-EPMC11274796 | biostudies-literature
Project description:BackgroundPatulin is a mycotoxin produced by Penicillium expansum, the causal agent of blue mold of stored pome fruits, and several other species of filamentous fungi. This mycotoxin has genotoxic, teratogenic and immunotoxic effects in mammals, and its presence in pome fruits and derived products represents a serious health hazard. Biocontrol agents in the Pucciniomycotina, such as the yeasts Sporobolomyces sp. strain IAM 13481 and Rhodosporidium kratochvilovae strain LS11, are able to resist patulin and degrade it into the less toxic compounds desoxypatulinic acid and ascladiol.ResultsIn this investigation we applied a transcriptomic approach based on RNAseq to annotate the genome of Sporobolomyces sp. IAM 13481 and then study the changes of gene expression in Sporobolomyces sp. exposed to patulin. Patulin treatment leads to ROS production and oxidative stress that result in the activation of stress response mechanisms controlled by transcription factors. Upregulated Sporobolomyces genes were those involved in oxidation-reduction and transport processes, suggesting the activation of defense mechanisms to resist patulin toxicity and expel the mycotoxin out of the cells. Other upregulated genes encoded proteins involved in metabolic processes such as those of the glutathione and thioredoxin systems, which are essential to restore the cellular redox homeostasis. Conversely, patulin treatment decreased the expression of genes involved in the processes of protein synthesis and modification, such as transcription, RNA processing, translation, protein phosphorylation and biosynthesis of amino acids. Also, genes encoding proteins involved in transport of ions, cell division and cell cycle were downregulated. This indicates a reduction of metabolic activity, probably due to the high energy requirement by the cells or metabolic arrest while recovering from the insult caused by patulin toxicity.ConclusionsComplex mechanisms are activated in a biocontrol yeast in response to patulin. The genes identified in this study can pave the way to develop i) a biodetoxification process of patulin in juices and ii) a biosensor for the rapid and cost-effective detection of this mycotoxin.
| S-EPMC4784387 | biostudies-literature
Project description:Abstract Patulin is a toxic secondary metabolite synthesized by various fungal strains. This mycotoxin is generally toxic to microorganisms as well as mammals due to its reactivity with the important cellular antioxidant glutathione. In this study, we explored the presence of microorganisms capable of degrading patulin. Microorganisms were screened for the ability to both grow in culture medium containing patulin and reduce its concentration. Screening of 510 soil samples resulted in the isolation of two filamentous fungal strains, one of which, Acremonium sp. TUS‐MM1 was characterized in detail. Liquid chromatography‐mass spectrometry and nuclear magnetic resonance analyses revealed that TUS‐MM1 cells degraded patulin to desoxypatulinic acid. In addition, extracellular components of strain TUS‐MM1 also exhibited patulin‐transforming activity. High‐performance liquid chromatography analysis revealed that the extracellular components generated several products from patulin. Disc diffusion assay using Escherichia coli cells revealed that the patulin‐transformation products by the extracellular components are less toxic than patulin. We also demonstrated that a thermostable, low‐molecular‐weight compound within the extracellular components was responsible for the patulin‐transforming activity. These results suggest that strain TUS‐MM1 transforms patulin into less‐toxic molecules by secreting a highly reactive compound. In addition, once patulin enters the cells, strain TUS‐MM1 can transform it into desoxypatulinic acid to reduce its toxicity. Filamentous fungi capable of degrading patulin were isolated. Acremonium sp. TUS‐MM1 transforms patulin into less‐toxic molecules by secreting a highly reactive compound. In addition, once patulin enters the cells, strain TUS‐MM1 can transform it into desoxypatulinic acid to reduce its toxicity.
| S-EPMC10415752 | biostudies-literature
Project description:Patulin (PAT) is a mycotoxin, with several acute, chronic, and cellular level toxic effects, produced by various fungi. A limit for PAT in food of has been set by authorities to guarantee food safety. Research on PAT in tea has been very limited although tea is the second largest beverage in the world. In this paper, HPLC-DAD and GC-MS methods for analysis of PAT in different tea products, such as non-fermented (green tea), partially fermented (oolong tea, white tea, yellow tea), completely fermented (black tea), and post-fermented (dark tea and Pu-erh tea) teas were developed. The methods showed good selectivity with regard to tea pigments and 5-hydroxymethylfurfural (5-HMF) and a recovery of 90-102% for PAT at a 10-100 ppb spiking level. Limit of detection (LOD) and limit of quantification (LOQ) in tea were 1.5 ng/g and 5.0 ng/g for HPLC-UV, and 0.25 ng/g and 0.83 ng/g for GC-MS. HPLC was simpler and more robust, while GC-MS showed higher sensitivity and selectivity. GC-MS was used to validate the HPLC-UV method and prove its accuracy. The PAT content of 219 Chinese tea samples was investigated. Most tea samples contained less than 10 ng/g, ten more than 10 ng/g and two more than 50 ng/g. The results imply that tea products in China are safe with regard to their PAT content. Even an extreme daily consumption of 25 g of the tea with the highest PAT content (124 ng/g), translates to an intake of only 3 μg/person/day, which is still an order of magnitude below the maximum allowed daily intake of 30 µg for an adult.
| S-EPMC9103431 | biostudies-literature
Project description:BackgroundSurgical resection followed by chemo-radiation postpones glioblastoma (GBM) progression and extends patient survival, but these tumours eventually recur. Multimodal treatment plans combining intraoperative techniques that maximise tumour excision with therapies aiming to remodel the immunologically cold GBM microenvironment could improve patients' outcomes. Herein, we report that targeted photoimmunotherapy (PIT) not only helps to define tumour location and margins but additionally promotes activation of anti-GBM T cell response.MethodsEGFR-specific affibody molecule (ZEGFR:03115) was conjugated to IR700. The response to ZEGFR:03115-IR700-PIT was investigated in vitro and in vivo in GBM cell lines and xenograft model. To determine the tumour-specific immune response post-PIT, a syngeneic GBM model was used.ResultsIn vitro findings confirmed the ability of ZEGFR:03115-IR700 to produce reactive oxygen species upon light irradiation. ZEGFR:03115-IR700-PIT promoted immunogenic cell death that triggered the release of damage-associated molecular patterns (DAMPs) (calreticulin, ATP, HSP70/90, and HMGB1) into the medium, leading to dendritic cell maturation. In vivo, therapeutic response to light-activated conjugate was observed in brain tumours as early as 1 h post-irradiation. Staining of the brain sections showed reduced cell proliferation, tumour necrosis, and microhaemorrhage within PIT-treated tumours that corroborated MRI T2*w acquisitions. Additionally, enhanced immunological response post-PIT resulted in the attraction and activation of T cells in mice bearing murine GBM brain tumours.ConclusionsOur data underline the potential of ZEGFR:03115-IR700 to accurately visualise EGFR-positive brain tumours and to destroy tumour cells post-conjugate irradiation turning an immunosuppressive tumour environment into an immune-vulnerable one.
| S-EPMC8780306 | biostudies-literature
Project description:The effect of mycotoxin patulin (4-hydroxy-4H-furo [3,2c] pyran-2 [6H] -one) on the mitochondrial carnitine/acylcarnitine carrier (CAC, SLC25A20) was investigated. Transport function was measured as [3H]-carnitineex/carnitinein antiport in proteoliposomes reconstituted with the native protein extracted from rat liver mitochondria or with the recombinant CAC over-expressed in E. coli. Patulin (PAT) inhibited both the mitochondrial native and recombinant transporters. The inhibition was not reversed by physiological and sulfhydryl-reducing reagents, such as glutathione (GSH) or dithioerythritol (DTE). The IC50 derived from the dose-response analysis indicated that PAT inhibition was in the range of 50 µM both on the native and on rat and human recombinant protein. The kinetics process revealed a competitive type of inhibition. A substrate protection experiment confirmed that the interaction of PAT with the protein occurred within a protein region, including the substrate-binding area. The mechanism of inhibition was identified using the site-directed mutagenesis of CAC. No inhibition was observed on Cys mutants in which only the C136 residue was mutated. Mass spectrometry studies and in silico molecular modeling analysis corroborated the outcomes derived from the biochemical assays.
| S-EPMC9917099 | biostudies-literature
Project description:Patulin is a mycotoxin that contaminates pome fruits and derived products worldwide. Basidiomycete yeasts belonging to the subphylum Pucciniomycotina have been identified to have the ability to degrade this molecule efficiently and have been explored through different approaches to understand this degradation process. In this study, Sporobolomyces sp. strain IAM 13481 was found to be able to degrade patulin to form two different breakdown products, desoxypatulinic acid and (Z)-ascladiol. To gain insight into the genetic basis of tolerance and degradation of patulin, more than 3,000 transfer DNA (T-DNA) insertional mutants were generated in strain IAM 13481 and screened for the inability to degrade patulin using a bioassay based on the sensitivity of Escherichia coli to patulin. Thirteen mutants showing reduced growth in the presence of patulin were isolated and further characterized. Genes disrupted in patulin-sensitive mutants included homologs of Saccharomyces cerevisiae YCK2, PAC2, DAL5, and VPS8. The patulin-sensitive mutants also exhibited hypersensitivity to reactive oxygen species as well as genotoxic and cell wall-destabilizing agents, suggesting that the inactivated genes are essential for tolerating and overcoming the initial toxicity of patulin. These results support a model whereby patulin degradation occurs through a multistep process that includes an initial tolerance to patulin that utilizes processes common to other external stresses, followed by two separate pathways for degradation.
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Project description:Chronic stress is known to promote inflammatory bowel disease (IBD), but the underlying mechanism remains largely unresolved. Here, we found chronic stress to sensitize mice to dextran sulfate sodium (DSS)-induced colitis; to increase the infiltration of B cells, neutrophils, and proinflammatory ly6Chi macrophages in colonic lamina propria; and to present with decreased thymus and mesenteric lymph node (MLN) coefficients. Circulating total white blood cells were significantly increased after stress, and the proportion of MLN-associated immune cells were largely changed. Results showed a marked activation of IL-6/STAT3 signaling by stress. The detrimental action of stress was not terminated in IL-6-/- mice. Interestingly, the composition of gut microbiota was dramatically changed after stress, with expansion of inflammation-promoting bacteria. Furthermore, results showed stress-induced deficient expression of mucin-2 and lysozyme, which may contribute to the disorder of gut microbiota. Of note is that, in the case of cohousing, the stress-induced immune reaction and decreased body weight were abrogated, and transferred gut microbiota from stressed mice to control mice was sufficient to facilitate DSS-induced colitis. The important role of gut microbiota was further reinforced by broad-spectrum antibiotic treatment. Taken together, our results reveal that chronic stress disturbs gut microbiota, triggering immune system response and facilitating DSS-induced colitis.
| S-EPMC5879702 | biostudies-literature
Project description:Purpose of reviewImmune checkpoint blockade targeting PD-1 and PD-L1 improves immune recognition of tumor cells but had only modest success in gynecological cancers as monotherapy. Growing focus has been placed on combination immunotherapy strategies to overcome this resistance, and this review serves to discuss some of the most promising studies in gynecological cancers.Recent findingsPD-1- and PD-L1-targeting antibodies are being combined with many novel agents including anti-CTLA-4 antibodies, PARP inhibitors, targeted agents, and traditional chemotherapy in promising studies with the hopes of increasing the immune response and overcoming resistance by targeting other pathways. Novel immune techniques including vaccines and adoptive cell therapies are also being implemented in gynecological cancers. Immune checkpoint combinations and novel immunotherapy strategies have demonstrated potential to overcome resistance to PD-1/PD-L1 blockade in gynecological cancers. Identification of biomarkers of response and resistance is a priority to tailor specific combination therapies to the appropriate patients.
| S-EPMC6244932 | biostudies-literature
Project description:Chemical cues play important roles in predator-prey interactions. Semiochemicals can aid predator foraging and alert prey organisms to the presence of predators. Previous work suggests that predator traits differentially influence prey behavior, however, empirical data on how prey organisms respond to chemical cues from predator species with different hunting strategies, and how foraging predators react to cues from potential competitors, is lacking. Furthermore, most research in this area has focused on aquatic and aboveground terrestrial systems, while interactions among belowground, soiling-dwelling organisms have received relatively little attention. Here, we assessed how chemical cues from three species of entomopathogenic nematodes (EPNs), each with a different foraging strategy, influenced herbivore (cucumber beetle) and natural enemy (EPN) foraging behavior. We predicted these cues could serve as chemical indicators of increased predation risk, prey availability, or competition. Our findings revealed that foraging cucumber beetle larvae avoided chemical cues from Heterorhabditis bacteriophora (active-foraging cruiser EPNs), but not Steinernema carpocapsae (ambusher EPNs) or Steinernema riobrave (intermediate-foraging EPNs). In contrast, foraging H. bacteriophora EPNs were attracted to cues produced by the two Steinernema species but not conspecific cues. Notably, the three EPN species produced distinct blends of olfactory cues, with only a few semi-conserved compounds across species. These results indicate that a belowground insect herbivore responds differently to chemical cues from different EPN species, with some EPN species avoiding prey detection. Moreover, the active-hunting EPNs were attracted to heterospecific cues, suggesting these cues indicate a greater probability of available prey, rather than strong interspecific competition.
| S-EPMC8613145 | biostudies-literature