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The food industry is unceasingly searching for accurate ways to check food safety. The presence of microbial toxins such as bacterial toxins, fungal toxins, and algal toxins in food products has become a concerning issue worldwide. These toxins can contaminate food during various stages of its production, transportation, and storage, posing a serious threat to human health. The reliable and quick determination of microbial toxins has become significant for eliminating the disease outbreaks caused by contaminated foodstuffs. Thus, there is an increased interest in developing low-cost and high-throughput sensors for the determination of microbial toxins in food matrices. Recently, fluorescent sensors have gained importance as one of the effective alternatives in food safety monitoring. The use of nanomaterials in the fabrication of fluorescent sensors has imparted amazing properties such as high selectivity and sensitivity, rapid results, good stability, and reproducibility to analyze microbial toxins in real food matrices. The present review summarizes the recent developments in nanomaterial-based fluorescent sensors for the detection of microbial toxins in food products. The review delves into the details of various fluorescent nanomaterials such as metal-based nanomaterials, upconversion nanoparticles, semiconductor quantum dots, carbon-based nanomaterials, and luminescent metal-organic frameworks describing their unique properties, advantages, drawbacks, and applications in the detection of microbial toxins in food products. Also, the performance comparison of the fluorescent nanomaterials in the detection of these toxins has been discussed. Further, the commercial aspects of fluorescent nanosensors for the detection of microbial toxins have been included, along with the future insights and challenges associated with microbial toxin detection. [ABSTRACT FROM AUTHOR]

Silage has been identified as a source of different microbial toxins, that may impair farm animal health and productivity as human health can also be compromised. In this sense, the aim of this study was to determine the impact of silage additives on the concentrations of deoxynivalenol (DON) and zearalenone (ZEN) mycotoxins and, eventually, to evaluate the hygienic quality of orchardgrass (Dactylis glomerata L.) silage based on the concentration of them compared to control silage. This study evaluated the influence of biological and chemical additives used in six different varieties of orchardgrass silage on DON and ZEN mycotoxin contents for the first time. The content of both fusariotoxins (DON and ZEN) in fresh matter and grass silage were below the threshold stipulated by the European Commission. The concentration of DON ranges from ~21.86 to 37.26 ng/kg, ~10.21 to 15 ng/kg, ~20.72 to 29.14 ng/kg; and ZEN range from ~3.42 to 7.87 ng/kg, ~3.85 to 8.62 ng/kg and ~2.15 to 5.08 ng/kg, in control, biological and chemical silages, respectively. In general, the biological additive was more efficient for preventing DON contamination, whereas the chemical additive was more efficient for preventing ZEN contamination in grass silage. In summary, the results obtained in this work demonstrate that biological and chemical additives can inhibit fungal growth and mycotoxin production on Dactylis glomerata L. silage and whose use could prevent animal and human diseases. [ABSTRACT FROM AUTHOR]

Secretion systems play a crucial role in microbe-microbe or host-microbe interactions. Among these systems, the extracellular contractile injection system (eCIS) is a unique bacterial and archaeal extracellular secretion system that injects protein toxins into target organisms. However, the specific proteins that eCISs inject into target cells and their functions remain largely unknown. Here, we developed a machine learning classifier to identify eCIS-associated toxins (EATs). The classifier combines genetic and biochemical features to identify EATs. We also developed a score for the eCIS N-terminal signal peptide to predict EAT loading. Using the classifier we classified 2,194 genes from 950 genomes as putative EATs. We validated four new EATs, EAT14-17, showing toxicity in bacterial and eukaryotic cells, and identified residues of their respective active sites that are critical for toxicity. Finally, we show that EAT14 inhibits mitogenic signaling in human cells. Our study provides insights into the diversity and functions of EATs and demonstrates machine learning capability of identifying novel toxins. The toxins can be employed in various applications dependently or independently of eCIS. Synopsis: Toxins delivered by the extracellular contractile injection system (eCIS) of 950 microbial genomes were identified using XGBoost classifier algorithm, four of which were experimentally confirmed and functionally characterized. eCIS is a poorly studied microbial toxin delivery system encoded by many environmental microbes. The first algorithm for predicting eCIS-associated toxins (EATs) was developed using genomic and biochemical features, and was used to identify ~2,200 EATs from 950 genomes. Features characterizing the N terminal signal peptide of EATs were identified and combined into a signal peptide score. Four new EATs genes (EAT14-17) were experimentally validated as being toxins, and critical EAT residues within the predicted catalytic sites were identified. EAT14 inhibits SRE-dependent mitogenic signaling in HEK293T cells. Toxins delivered by the extracellular contractile injection system (eCIS) of 950 microbial genomes were identified using XGBoost classifier algorithm, four of which were experimentally confirmed and functionally characterized. [ABSTRACT FROM AUTHOR]

Abstract Secretion systems play a crucial role in microbe-microbe or host-microbe interactions. Among these systems, the extracellular contractile injection system (eCIS) is a unique bacterial and archaeal extracellular secretion system that injects protein toxins into target organisms. However, the specific proteins that eCISs inject into target cells and their functions remain largely unknown. Here, we developed a machine learning classifier to identify eCIS-associated toxins (EATs). The classifier combines genetic and biochemical features to identify EATs. We also developed a score for the eCIS N-terminal signal peptide to predict EAT loading. Using the classifier we classified 2,194 genes from 950 genomes as putative EATs. We validated four new EATs, EAT14-17, showing toxicity in bacterial and eukaryotic cells, and identified residues of their respective active sites that are critical for toxicity. Finally, we show that EAT14 inhibits mitogenic signaling in human cells. Our study provides insights into the diversity and functions of EATs and demonstrates machine learning capability of identifying novel toxins. The toxins can be employed in various applications dependently or independently of eCIS.

Increasing the number of resistant bacteria resistant to treatment is one of the leading causes of death worldwide. These bacteria are created in wounds and injuries and can be transferred through hospital equipment. Various attempts have been made to treat these bacteria in recent years, such as using different drugs and new sterilization methods. However, some bacteria resist drugs, and other traditional methods cannot destroy them. In the meantime, various studies have shown that cold atmospheric plasma can kill these bacteria through different mechanisms, making cold plasma a promising tool to deactivate bacteria. This new technology can be effectively used in the food industry because it has the potential to inactivate microorganisms such as spores and microbial toxins and increase the wettability and printability of polymers to pack fresh and dried food. It can also increase the shelf life of food without leaving any residue or chemical effluent. This paper investigates cold plasma's potential, advantages, and disadvantages in the food industry and sterilization. [ABSTRACT FROM AUTHOR]

Insect host defense comprises two complementary dimensions, microbial killing-mediated resistance and microbial toxin neutralization-mediated resilience, both jointly providing protection against pathogen infections. Insect defensins are a class of effectors of innate immunity primarily responsible for resistance to Gram-positive bacteria. Here, we report a newly originated gene from an ancestral defensin via genetic deletion following gene duplication in Drosophila virilis, which confers an enhanced resilience to Gram-positive bacterial infection. This gene encodes an 18-mer arginine-rich peptide (termed DvirARP) with differences from its parent gene in its pattern of expression, structure and function. DvirARP specifically expresses in D. virilis female adults with a constitutive manner. It adopts a novel fold with a 310 helix and a two CXC motif-containing loop stabilized by two disulfide bridges. DvirARP exhibits no activity on the majority of microorganisms tested and only a weak activity against two Gram-positive bacteria. DvirARP knockout flies are viable and have no obvious defect in reproductivity but they are more susceptible to the DvirARP-resistant Staphylococcus aureus infection than the wild type files, which can be attributable to its ability in neutralization of the S. aureus secreted toxins. Phylogenetic distribution analysis reveals that DvirARP is restrictedly present in the Drosophila subgenus, but independent deletion variations also occur in defensins from the Sophophora subgenus, in support of the evolvability of this class of immune effectors. Our work illustrates for the first time how a duplicate resistance-mediated gene evolves an ability to increase the resilience of a subset of Drosophila species against bacterial infection. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus strains that produce the toxin Panton-Valentine leukocidin (PVL-SA) frequently cause recurrent skin and soft tissue infections. PVL binds to and kills human neutrophils, resulting in the formation of neutrophil extracellular traps (NETs), but the pathomechanism has not been extensively studied. Furthermore, it is unclear why some individuals colonized with PVL-SA experience recurring infections whereas others are asymptomatic. We thus aimed to (1) investigate how PVL exerts its pathogenicity on neutrophils and (2) identify factors that could help to explain the predisposition of patients with recurring infections. We provide genetic and pharmacological evidence that PVL-induced NET formation is independent of NADPH oxidase and reactive oxygen species production. Moreover, through NET proteome analysis we identified that the protein content of PVL-induced NETs is different from NETs induced by mitogen or the microbial toxin nigericin. The abundance of the proteins cathelicidin (CAMP), elastase (NE), and proteinase 3 (PRTN3) was lower on PVL-induced NETs, and as such they were unable to kill S. aureus. Furthermore, we found that neutrophils from affected patients express higher levels of CD45, one of the PVL receptors, and are more susceptible to be killed at a low PVL concentration than control neutrophils. Neutrophils from patients that experience recurring PVL-positive infections may thus be more sensitive to PVL-induced NET formation, which might impair their ability to combat the infection. [ABSTRACT FROM AUTHOR]

Abstract Microbial toxins are important factors that contribute to human diseases and food losses. Predicting the production of these toxins before they occur is a significant challenge. In this study, we innovatively developed a strategy called targeted acquisition of toxin‐related immunogen (TATRI) to identify early diagnostic biomarkers for microbial toxins. Taking Aspergillus flavus as an example, we employed an immunoassay‐based screening approach to identify nanobodies that exhibited significant response signals to different toxigenic strains. Subsequently, we isolated and purified the specific immunogen pre‐aflatoxin biomarker PAB‐01 that bound to the selected nanobody. The results showed that the level of PAB‐01 was positively correlated with the toxin‐producing ability of A. flavus strains and could be detected before the production of aflatoxins. It met the essential requirements as an early diagnostic biomarker for aflatoxin contamination. Protein identification and bioinformatics analysis revealed that PAB‐01 is a glycoprotein that can be secreted into the extracellular space. It is located on chromosome 5 of A. flavus and belongs to the 75 family of glycoside hydrolases. Furthermore, we used 7 g/kg as the critical concentration of PAB‐01 to diagnose the risk of aflatoxin contamination in stored peanuts, with an accuracy rate of 75.9% for high‐risk samples. In summary, this work provides a promising approach for the identification of protein biomarkers prior to microbial toxin production and the establishment of early diagnostic techniques for microbial toxins.

Almonds play a significant role in Iran's economy, and factors that threaten their market, such as aflatoxins, need careful consideration. Plasma-activated water (PAW) is a new method that has antioxidant activity and can eliminate toxins and microbial agents, making it a suitable solution for removing aflatoxins from almonds. In a study, the continuous PAW production system was used to control and remove almond aflatoxins, and molecular dynamics simulation was employed to evaluate the impact of PAW on aflatoxin B1. The study found that reducing the flow rate of plasma-treated water had the greatest effect on reducing aflatoxin concentration, followed by PAW application time, the dose of inoculated toxin, and the air/gas mixture ratio. The use of PAW reduced aflatoxin concentration in almonds by 12% to 56.8%. The simulation results suggested that PAW can affect the structure of aflatoxin B1, change and destroy its activity, and reduce its toxicity. Among the free radicals tested, NO3− was found to be the most effective in degrading aflatoxin B1. This study demonstrates the potential of PAW as a method to remove aflatoxins and enhance the safety of almonds. [ABSTRACT FROM AUTHOR]

ABSTRACTProtein toxins are key molecular weapons in biology that are used to attack neighboring cells. Bacteria use protein toxins to kill or inhibit the growth of prokaryotic and eukaryotic cells using various modes of action that target essential cellular components. The toxins are responsible for shaping microbiomes in different habitats, for abortive phage infection, and for severe infectious diseases in animals and plants. Although several toxin databases have been developed, each one is devoted to a specific toxin family, and they encompass a relatively small number of toxins. Antimicrobial toxins are often accompanied by antitoxins (or immunity proteins) that neutralize the cognate toxins. Here, we combined toxins and antitoxins from many resources and created Toxinome, a comprehensive and updated bacterial protein toxin database. The Toxinome includes a total of 1,483,028 toxins and 491,345 antitoxins encoded in 59,475 bacterial genomes across the tree of life. We identified a depletion of toxin and antitoxin genes in bacteria that dwell in extreme temperatures. We defined 5,161 unique Toxin Islands within phylogenetically diverse bacterial genomes, which are loci dense in toxin and antitoxin genes. By focusing on the unannotated genes within these islands, we characterized a number of these genes as toxins or antitoxins. Finally, we developed an interactive Toxinome website (http://toxinome.pythonanywhere.com) that allows searching and downloading of our database. The Toxinome resource will be useful to the large research community interested in bacterial toxins and can guide toxin discovery and function elucidation, and infectious disease diagnosis and treatment.IMPORTANCEMicrobes use protein toxins as important tools to attack neighboring cells, microbial or eukaryotic, and for self-killing when attacked by viruses. These toxins work through different mechanisms to inhibit cell growth or kill cells. Microbes also use antitoxin proteins to neutralize the toxin activities. Here, we developed a comprehensive database called Toxinome of nearly two million toxins and antitoxins that are encoded in 59,475 bacterial genomes. We described the distribution of bacterial toxins and identified that they are depleted by bacteria that live in hot and cold temperatures. We found 5,161 cases in which toxins and antitoxins are densely clustered in bacterial genomes and termed these areas “Toxin Islands.” The Toxinome database is a useful resource for anyone interested in toxin biology and evolution, and it can guide the discovery of new toxins.

The need for more effective and precision medicines for cancer has pushed the exploration of new materials appropriate for drug delivery and imaging, and alternative receptors for targeting. Among the most promising strategies, finding suitable cell surface receptors and targeting agents for cancer-associated platelet derived growth factor receptor β (PDGFR-β)+ stromal fibroblasts is highly appealing. As a neglected target, this cell type mechanically and biologically supports the growth, progression, and infiltration of solid tumors in non-small cell lung, breast, pancreatic, and colorectal cancers. We have developed a family of PDGFR-β-targeted nanoparticles based on biofabricated, self-assembling proteins, upon hierarchical and iterative selective processes starting from four initial candidates. The modular protein PDGFD-GFP-H6 is well produced in recombinant bacteria, resulting in structurally robust oligomeric particles that selectively penetrates into PDGFR-β+ stromal fibroblasts in a dose-dependent manner, by means of the PDGFR-β ligand PDGFD. Upon in vivo administration, these GFP-carrying protein nanoparticles precisely accumulate in tumor tissues and enlighten them for IVIS observation. When GFP is replaced by a microbial toxin, selective tumor tissue destruction is observed associated with a significant reduction in tumor volume growth. The presented data validate the PDGFR-β/PDGFD pair as a promising toolbox for targeted drug delivery in the tumor microenvironment and oligomeric protein nanoparticles as a powerful instrument to mediate highly selective biosafe targeting in cancer through non-cancer cells. We have developed a transversal platform for nanoparticle-based drug delivery into cancer-associated fibroblasts. This is based on the engineered modular protein PDGFD-GFP-H6 that spontaneously self-assemble and selectively penetrates into PDGFR-β+ stromal fibroblasts in a dose-dependent manner, by means of the PDGFR-β ligand PDGFD. In vivo , these protein nanoparticles accumulate in tumor and when incorporating a microbial toxin, they destroy tumor tissues with a significant reduction in tumor volume, in absence of side toxicities. The data presented here validate the PDGFR-β/PDGFD pair as a fully versatile toolbox for targeted drug delivery in the tumor microenvironment intended as a synergistic treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

• During infection, plants suffer with many physiological and biochemical changes. • Antioxidants and secondary metabolites defend plants against biotic stress. • Regulation of antioxidant defense is an essential component of defense. • Plants characteristically produce cellular antioxidants for cellular protection. • Extensive effects in the complete networks in plants are needed for the analyzed genes. Plants, being sessile in nature, are inept to escape biotic stress that adversely impact their growth, development, and productivity. Rather, plants employ a variety of processes at the molecular, morphological, physiological as well as biochemical levels to mitigate the negative impacts of such stressors. Plants have a complex defense system against pathogens, pests and diseases, which includes collaborative actions regulated by array of genes and transcription factors. Immunity against pathogenic attack is determined by the plant's ability to avoid early infection and limit the growth of harmful pathogens, whereas resistance to microbial toxins is determined by the capacity of plant tissues to reduce toxin accumulation and its detoxification. This ability can be achieved through modulations in multiple processes. Among these processes, regulation of the antioxidant defense system, generation of reactive oxygen species and production of secondary metabolites is reckoned as an essential component of defense mechanism. Antioxidants such as superoxide dismutase (SOD), peroxidase (POD) and secondary metabolites, specifically phenolics, terpenes, and nitrogen-containing compounds have been widely proven to defend plants against range of biotic stresses. It is essentially needed to improve existing management practices to control pathogens and breed immunity in crops for sustainable agriculture and food security. Particularly to improve resistance to pathogenesis, the breeding of long-term resilience in cereals genotypes is one of the most promising strategies. A better grasp of the molecular processes underlying plant resilience to microbial assault will cast light on plant-pathogen interactions and provide useful information for breeding programs. This review emphasizes the ongoing investigation and significant operation of key molecular, physiological, and biochemical factors for tolerance and resistance in Oryza sativa against microbial infections. Additionally, we have focused on secondary metabolites and antioxidant defense system playing a crucial role in deciding how plants react to pathogen attacks. [ABSTRACT FROM AUTHOR]

Doenjang and ganjang are traditional, Korean fermented foods. They are manufactured by fermenting jangs, either through the traditional natural fermentation, using straw, or the commercial inoculating starter cultures. However, both Bacillus cereus and aflatoxins have been detected in jangs, compromising their safety. Aflatoxins have been detected on numerous occasions. However, studies are yet to be conducted on whether these safety issues differ depending on the manufacturing method. In this study, we evaluated whether the manufacturing methods of doenjang and ganjang alter their safety. Samples of traditional and commercial doenjang and ganjang were analyzed for aflatoxin and B. cereus contamination. Microbiome taxonomic profiling was performed to assess microbial composition. The experimental methodology involved sample collection from various stages of production, including the use of starter cultures and natural fermentation processes. Aflatoxin levels were determined using regulatory limits, and B. cereus content was evaluated against specific thresholds. Aflatoxins were detected in both traditional and commercial doenjang and ganjang, with either the total aflatoxin (15 μg/kg) or aflatoxin B1 (10 μg/kg) exceeding the regulatory limits. However, ochratoxin A was not detected in any of the samples. B. cereus was detected in some samples, within the regulatory limit (4 log CFU/g), and was not influenced by the manufacturing method. Analysis at the production stage showed that aflatoxin increased alongside the fermentation time in traditional doenjang. However, in ganjang, no significant differences were associated with the fermentation period. When using starter cultures, the fermentation period did not affect the toxin level in both foods. Both methods showed lower aflatoxin content in the initial doenjang and ganjang samples than in meju. B. cereus was not detected in either method, as its content decreased over the fermentation period. Microbiome taxonomic profiling confirmed that even when using starter cultures, B. cereus was not a dominant species and was considerably affected by the environment. Staphylococcus aureus and Pseudomonas, pathogenic in nature, were detected in products manufactured using the traditional method; hence, the potential risk of this method was higher than that of the commercial method. The experimental methodology employed in this study contributes to understanding the microbial composition and toxin contamination levels in doenjang and ganjang, contributing to the overall knowledge of their safety and quality control. [ABSTRACT FROM AUTHOR]

Context: Some studies have investigated the application of sunflower meal (SFM) in feeding livestock and poultry. However, there have been few researches related to fermenting SFM. Aims: In this experiment, the neutral detergent fibre degradability and increase rate of crude protein were used as rapid evaluation indicators of solid-state fermentation (SSF), and the response-surface methodology was used to optimise the process conditions for SSF of SFM with the mixed fermentation agent (Bacillus subtilis H-12, Saccharomyces cerevisiae Y-5 and Trichoderma longibrachiatum). Methods: Box-Behnken design with three factors and three levels was adopted. The process conditions were fermentation temperature (28°C, 32°C, 36°C), duration of time (48 h, 72 h, 96 h), and moisture to substrate ratio (MSR; 50 %, 100%, 150 % (v/m)). The nutritional quality and feeding value of the original SFM and fermented SFM were evaluated under the optimal process conditions according to response-surface methodology. Key results: The results showed that the optimal process conditions for SSF of SFM were as follows: fermentation temperature 31.7°C, duration of time 72.2 h, and MSR 106.4%; the contents of crude protein (44.82%), true protein (42.40%) and total amino acid (36.77%) in fermented SFM were significantly increased compared with those of original SFM (P < 0.05); the neutral detergent fibre, crude fibre and chlorogenic acid contents were decreased significantly (P < 0.05); the index values of metal elements, vomitoxin, aflatoxin and coliform were all lower than the national limit standards. Conclusion: The nutritional quality and feeding value of SFM were improved by microbial SSF, while the potential risks of harmful toxins and microbial contamination were reduced. Implications: The results of this study will contribute to the research on the development of protein-feed raw materials and explore the application of SFM in feed industry. Some studies have investigated the application of sunflower meal (SFM) on feeding livestock poultry. However, there have been few researches related to ferment SFM. In this experiment, the solid-state fermentation process of SFM was optimised. The results showed that the nutritional quality and feeding value of SFM were improved by microbial SSF. The results of this study will contribute to the research on the development of protein-feed raw materials for animals and explore the application of SFM. [ABSTRACT FROM AUTHOR]

Clostridioides difficile (C. difficile) toxins A (TcdA) and B (TcdB) cause antibiotic-associated colitis in part by disrupting epithelial barrier function. Accurate in vitro models are necessary to detect early toxicity kinetics, investigate disease etiology, and develop preclinical models for new therapies. Properties of cancer cell lines and organoids inherently limit these efforts. We developed adult stem cell-derived monolayers of differentiated human colonic epithelium (hCE) with barrier function, investigated the impact of toxins on apical/ basal aspects of monolayers, and evaluated whether a leaky epithelial barrier enhances toxicity. Single-cell RNA-sequencing (scRNAseq) mapped C. difficile-relevant genes to human lineages. Transcriptomics compared hCE to Caco-2, informed timing of in vitro stem cell differentiation, and revealed transcriptional responses to TcdA. Transepithelial electrical resistance (TEER) and fluorescent permeability assays measured cytotoxicity. Contribution of TcdB toxicity was evaluated in a diclofenac-induced leaky gut model. scRNAseq demonstrated broad and variable toxin receptor expression. Absorptive colonocytes in vivo displayed increased toxin receptor, Rho GTPase, and cell junction gene expression. Advanced TcdA toxicity generally decreased cytokine/chemokine and increased tight junction and death receptor genes. Differentiated Caco-2 cells remained immature whereas hCE monolayers were similar to mature colonocytes in vivo. Basal exposure of TcdA/B caused greater toxicity and apoptosis than apical exposure. Apical exposure to toxins was enhanced by diclofenac. Apical/basal toxicities are uncoupled with more rapid onset and increased magnitude postbasal toxin exposure. Leaky junctions enhance toxicity of apical TcdB exposure. hCE monolayers represent a physiologically relevant and sensitive system to evaluate the impact of microbial toxins on gut epithelium. [ABSTRACT FROM AUTHOR]

It can cause scattered dust and usually loaded with various germs that adversely affect the health of silos workersin silos. The main objective of the study is to measure microbial contamination. (bacterial, fungal, mycotoxins), which are widely prevalent in Iraqi silos and mills and negatively It affects the health of silos workers in particular and the general health of the community. The study included 40 samples of wheat grains and 40 samples of wheat flour, which were randomly collected for the winter seasons from 4 silos in Baghdad, silo Maysan and siloAL- Basra, and silo Erbil and silo Kirkuk during December and January 2022. The results indicated that the most isolated types of wheat and wheat flour are pathological spores in addition to the presence of a percentage of microbial toxins, and the chemical analysis with HPLC during the winter season showed the presence of toxic mycotoxin contamination for a number of silos, and the khan was about (76.6 ppb) by 12.5%, while the silos (cycle, coronary) were about 37.5%, with statistically significant differences (p. ≤ 0.05). The results of the statistical analysis indicated that there were statistically Statistically significant differences (p≤0.05) were recorded for wheat and flour in (temperature and humidity associated with storage,) and most of them samples contained more Coliforms and Mold than the permissible limit, while some of the samples contained an allowable percentage of mycotoxins. [ABSTRACT FROM AUTHOR]

The lung microbiome plays an essential role in maintaining healthy lung function, including host immune homeostasis. Lung microbial dysbiosis or disruption of the gut-lung axis can contribute to lung carcinogenesis by causing DNA damage, inducing genomic instability, or altering the host's susceptibility to carcinogenic insults. Thus far, most studies have reported the association of microbial composition in lung cancer. Mechanistic studies describing host-microbe interactions in promoting lung carcinogenesis are limited. Considering cancer as a multifaceted disease where epigenetic dysregulation plays a critical role, epigenetic modifying potentials of microbial metabolites and toxins and their roles in lung tumorigenesis are not well studied. The current review explains microbial dysbiosis and epigenetic aberrations in lung cancer and potential therapeutic opportunities. [ABSTRACT FROM AUTHOR]

[Display omitted] It is a major concern to treat cancer successfully, due to the distinctive pathophysiology of cancer cells and the gradual manifestation of resistance. Specific action, adverse effects and development of resistance has prompted the urgent requirement of exploring alternative anti-tumour treatment therapies. The naturally derived microbial toxins as a therapy against cancer cells are a promisingly new dimension. Various important microbial toxins such as Diphtheria toxin, Vibrio cholera toxin, Aflatoxin, Patulin, Cryptophycin-55, Chlorella are derived from several bacterial, fungal and algal species. These agents act on different biotargets such as inhibition of protein synthesis, reduction in cell growth, regulation of cell cycle and many cellular processes. Bacterial toxins produce actions primarily by targeting protein moieties and some immunomodulation and few acts through DNA. Fungal toxins appear to have more DNA damaging activity and affect the cell cycle. Algal toxins produce alteration in mitochondrial phosphorylation. In conclusion, microbial toxins and their metabolites appear to have a great potential to provide a promising option for the treatment and management to combat cancer. [ABSTRACT FROM AUTHOR]

The MqsRA toxin-antitoxin system is a component of the Escherichia coli stress response. Free MqsR, a ribonuclease, cleaves mRNAs containing a 50-GC-30 sequence causing a global shutdown of translation and the cell to enter a state of dormancy. Despite a general understanding of MqsR function, the molecular mechanism(s) by which MqsR binds and cleaves RNA and how one or more of these activities is inhibited by its cognate antitoxin MqsA is still poorly understood. Here, we used NMR spectroscopy coupled with mRNA cleavage assays to identify the molecular mechanism of MqsR substrate recognition and the MqsR residues that are essential for its catalytic activity. We show that MqsR preferentially binds substrates that contain purines in the -2 and -1 position relative to the MqsR consensus cleavage sequence and that two residues of MqsR, Tyr81, and Lys56 are strictly required for mRNA cleavage. We also show that MqsA inhibits MqsR activity by sterically blocking mRNA substrates from binding while leaving the active site fully accessible to mononucleotides. Together, these data identify the residues of MqsR that mediate RNA cleavage and reveal a novel mechanism that regulates MqsR substrate specificity. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) contaminate the global marine and terrestrial ecosystems. This environmental contamination can enter the food chain, with MPs found in drinking water, fishery products and other food categories. Consequently, ingestion is considered the main route of human exposure to MPs. Concerns exist on the potential of MPs to act as vectors for pathogenic bacteria, possibly threatening microbial food safety. Starting from the current evidence on foodborne pathogens associated with MPs, we review the state of knowledge on the putative role of MPs in enhancing harmful bacterial traits and transporting them to humans. Finally, we focus on the simultaneous uptake of MPs and pathogens in the human gut. Overall, we identify major knowledge gaps, both on the mechanisms and the possible health outcomes. The scarce and inconclusive results regarding the effect of MPs on microbial virulence and evolution, together with the insufficient knowledge about the attachment of microbial toxins to MPs, highlight the need for further studies. We conclude that biofilm-coated MPs in foodstuffs may pose several risks to food safety, but further research will be essential to determine the extent of their effect on human health. [Display omitted] • Micro- and nanoplastics are present as contaminants in the food chain. • Foodborne pathogens and biotoxins have been identified on (micro)plastics biofilms. • Micro- and nanoplastics can affect bacterial virulence and other harmful traits. • The uptake of microplastics carrying pathogens may impact on human health. [ABSTRACT FROM AUTHOR]

Frequent contamination of foods with microbial toxins produced by microorganisms such as bacteria, fungi, and algae represents an increasing public health problem that requires the development of quick and easy tools to detect them at trace levels. Recently, it has been found that colorimetric detection methods may replace traditional methods in the field because of their ease of use, quick response, ease of manufacture, low cost, and naked-eye visibility. Therefore, it is suitable for fieldwork, especially for work in remote areas of the world. However, the development of colorimetric detection methods with low detection limits is a challenge that limits their wide applicability in the detection of food contaminants. To address these challenges, nanomaterial-based transduction systems are used to construct colorimetric biosensors. For example, gold nanoparticles (AuNPs) provide an excellent platform for the development of colorimetric biosensors because they offer the advantages of easy synthesis, biocompatibility, advanced surface functionality, and adjustable physicochemical properties. The selectivity of the colorimetric biosensor can be achieved by the combination of aptamers and gold nanoparticles, which provides an unprecedented opportunity to detect microbial toxins. Compared to antibodies, aptamers have significant advantages in the analysis of microbial toxins due to their smaller size, higher binding affinity, reproducible chemical synthesis and modification, stability, and specificity. Two colorimetric mechanisms for the detection of microbial toxins based on AuNPs have been described. First, sensors that use the localized surface plasmon resonance (LSPR) phenomenon of gold nanoparticles can exhibit very strong colors in the visible range because of changes caused by aggregation or disaggregation. Second, the detection mechanism of AuNPs is based on their enzyme mimetic properties and it is possible to construct a colorimetric biosensor based on the 3,3',5,5'-tetramethylbenzidine/Hydrogen peroxide, TMB/H2O2 reaction to detect microbial toxins. Therefore, this review summarizes the recent applications of AuNP-based colorimetric aptasensors for detecting microbial toxins, including bacterial toxins, fungal toxins, and algal toxins focusing on selectivity, sensitivity, and practicality. Finally, the most important current challenges in this field and future research opportunities are discussed. [ABSTRACT FROM AUTHOR]

The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of birth, diet, medication, ageing and chronic inflammation, can modify the intestinal microbiota. Chronic kidney disease (CKD) seems to have a direct and unique effect, as increased urea levels result in alteration of the gut microbiome, leading to overproduction of its metabolites. Therefore, potentially noxious microbial uremic toxins, which have predominantly renal clearance, including p-cresyl sulfate, indoxyl sulfate and N-oxide of trimethylamine [Trimethylamine-N-Oxide (TMAO)], accumulate in human's body, and are responsible not only for the clinical implications of CKD, but also for the progression of renal failure itself. Certain changes in gut microbiome are observed in patients with end stage renal disease (ESRD), either when undergoing hemodialysis or after kidney transplantation. The purpose of this review is to summarize the changes of gut microbiome and the protein bound uremic toxins which are observed in CKD and in different kidney replacement strategies. In addition, we attempt to review the connection between microbiome, clinical implications and immune response in CKD. [ABSTRACT FROM AUTHOR]

Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae) is a serious agro‐economic pest of cucurbits around the world. Management of tephritid fruit flies is till date mainly dependent on the use of chemical pesticides. In a rising concern about environment quality and rapid development of resistance in insect pests, biological control of insect pests is being contemplated, and in response, research approaches are constantly evolving. Various naturally occurring control agents of melon fruit fly such as parasitoids, bacteria, fungi and nematodes have potential in the management of Z. cucurbitae. Many parasitoids including Psyttalia fletcheri, Fopius arisanus, Dirhinus giffardii and Spalangia endius are known to attack various life stages of Z. cucurbitae. Although parasitoids are being principally exploited for control of Z. cucurbitae, various other entomopathogens such as fungi (Beauveria bassiana, Paecilomyces fumosoroseus, Metarhizium anisopliae), bacteria (Bacillus thuringiensis), nematodes (Heterorhabditis indica, Steinernema feltiae) and microbial toxins/products (spinosad, avermectin) are being investigated or used for biological control. The development of farming methodologies with greater credence on ecosystem services such as biological control of Z. cucurbitae will increase sustainability of agroecosystems. This review provides a concise compilation of these biological control agents along with their effectiveness and will help researchers in designing various integrated pest management strategies against Z. cucurbitae that involve biological control agents. [ABSTRACT FROM AUTHOR]

The development of robust bioanalytical devices and biosensors for infectious pathogens is progressing well with the advent of new materials, concepts, and technology. The progress is also stepping towards developing high throughput screening technologies that can quickly identify, differentiate, and determine the concentration of harmful pathogens, facilitating the decision-making process for their elimination and therapeutic interventions in large-scale operations. Recently, much effort has been focused on upgrading these analytical devices to an intelligent technological platform by integrating them with modern communication systems, such as the internet of things (IoT) and machine learning (ML), to expand their application horizon. This review outlines the recent development and applications of bioanalytical devices and biosensors to detect pathogenic microbes in environmental samples. First, the nature of the recent outbreaks of pathogenic microbes such as foodborne, waterborne, and airborne pathogens and microbial toxins are discussed to understand the severity of the problems. Next, the discussion focuses on the detection systems chronologically, starting with the conventional methods, advanced techniques, and emerging technologies, such as biosensors and other portable devices and detection platforms for pathogens. Finally, the progress on multiplex assays, wearable devices, and integration of smartphone technologies to facilitate pathogen detection systems for wider applications are highlighted. [ABSTRACT FROM AUTHOR]

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The microbial toxin β- N -methylamino-L-alanine (BMAA), which is derived from cyanobacteria, targets neuronal mitochondria, leading to the activation of neuronal innate immunity and, consequently, neurodegeneration. Although known to modulate brain inflammation, the precise role of aberrant microglial function in the neurodegenerative process remains elusive. To determine if neurons signal microglial cells, we treated primary cortical neurons with BMAA and then co-cultured them with the N9 microglial cell line. Our observations indicate that microglial cell activation requires initial neuronal priming. Contrary to what was observed in cortical neurons, BMAA was not able to activate inflammatory pathways in N9 cells. We observed that microglial activation is dependent on mitochondrial dysfunction signaled by BMAA-treated neurons. In this scenario, the NLRP3 pro-inflammatory pathway is activated due to mitochondrial impairment in N9 cells. These results demonstrate that microglia activation in the presence of BMAA is dependent on neuronal signaling. This study provides evidence that neurons may trigger microglia activation and subsequent neuroinflammation. In addition, we demonstrate that microglial activation may have a protective role in ameliorating neuronal innate immune activation, at least in the initial phase. This work challenges the current understanding of neuroinflammation by assigning the primary role to neurons. [Display omitted] • Microglia cells are resistant to BMAA neurotoxin. • BMAA-treated neurons signal microglia through the mitochondria and protein aggregates. • Mitochondrial dysfunction is required for microglia activation • Neuronal-mediated microglia activation reduces neuronal immune innate activation. • Neuron-microglia crosstalk is independent of cytokines release. [ABSTRACT FROM AUTHOR]

Currently, investigations on the microbiota of sports centers and related facilities have been carried out in some countries, which showed that Microsporum gypseum, Trichophyton mentagrophytes and T. tonsurans are important dermatoprotofungi. In China, some research on athletes and sports equipment between the fungal community and public health has made some interesting achievements. However, the bacterial group among them has not been reported. Therefore, The aim of this study was to uncover (I) gymnastic equipment is there potential pathogenic factors and (ii) is there any difference in the biomarker of bacterial in different types of gymnastic room? The samples were collected from the gymnastics halls of one university in western China and main sports equipment, including gymnastics carpets, moving barres, hoops and balls, as well as wall bars, parallel bars and horizontal bars. The 16S rDNA of all the samples was sequenced, and the analyses were performed using FaproTax, Bug base function prediction and Line Discriminant Analysis (LDA) Effect Size. A 16S rDNA sequence analysis revealed abundant bacterial species biodiversity on gymnasts and apparatuses from two gymnastics halls at a university in western China. An analysis using the FaproTax and Bugbase functional prediction platforms showed that there were some opportunistic pathogens on the athletes and equipment from the Rhythmic Gymnastics (RG) and Artistic Gymnastics (AG) halls, such as Staphylococcus and Corynebacteiaceae. Infectious agents associated with cancer induction and development, such as Ruminococcaceae, Veillonellaceae and Moraxellaceae, as well as microbial toxin producers with a potential impact on human health, were also detected. According to a line discriminant analysis (LDA effect size), the bacterial biomarker groups of the two gymnasiums were different at the phylum-genus level: for RG, Erysipelatoclostridium, Lachnospiraceae and Bacteroidales, while for AG, Rhizobiales. Based on the results of the investigation, we suggest that more comprehensive consideration should be given to indoor microbial biodiversity and related public health problems in school gymnasiums. [ABSTRACT FROM AUTHOR]

Inflammation is part of innate immunity and is a natural response of the body to bacteria, virus, and any other pathogen infections or to damaged tissues. However, too much inflammation or chronic inflammation contributes to a wide variety of diseases such as inflammatory bowel disease, cancer, type 2 diabetes, heart disease, and autoimmune diseases such as rheumatoid arthritis. Recent studies underscored the critical role of K+ and Cl- efflux in the activation of the inflammasome. The NLRP3 inflammasome is a multiprotein complex that mediates the production of the proinflammatory cytokines IL-1b and IL-18 and initiates the inflammatory cell death or pyroptosis. The NLRP3 inflammasome can be activated by multiple stimuli such as extracellular ATP, microbial toxins, ROS, mitochondrial DNA, or particulate matter. Although the precise mechanisms of NLRP3 activation and regulation by these diverse agonists remain unclear, multiple reports indicate that all NLRP3 agonists ultimately lead to a drop in intracellular concentration of potassium (K+ efflux) and chloride (Cl- efflux). The WNK-SPAK/OSR1-[N]KCC pathway plays a critical role in maintaining K+ and Cl- ion concentrations in the cell. Recent advances indicate that the WNK-SPAK-[N]KCC pathway plays a role in the activation of the innate immune response. This review highlights recent discoveries detailing how ion transport regulates innate immune cell response to inflammatory stimuli. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a chronic, progressive and second most prevalent neurological disorder affecting the motor system. Cardinal motor impairment and α-synucleinopathy are the characteristic features of PD. Recently, it has been identified that the gut-brain axis is substantially regulated by the gut microbiome (GM) through an immunological, neuroendocrine, and neural mechanism. However, disturbance in the gut-microbiome-brain axis in PD might proceed to gastrointestinal manifestations intermittently leading to the motor system and the PD pathogenesis itself. The gut microbial toxins may induce the production of α-synuclein (α-syn) aggregates in the enteric nervous system (ENS), which may proliferate and propagate in a prion-like-manner through the vagus nerve to the central nervous system (CNS); supporting the hypothesis that, GM might play a pivotal role in PD pathogenesis. Overstimulated innate immune system due to intestinal bacterial overgrowth or gut dysbiosis and the enhanced intestinal permeability may persuade systemic inflammation, while the activation of enteric glial cells and enteric neurons may contribute to α-synucleinopathy. Gut microbiota can bear a significant impact on neurological outcomes such as learning, memory and cognition. In this review paper, we summarize how the alterations in gut microbiota and ENS inflammation are associated with PD pathogenesis. The evidence supporting the causative role played by gut-associated dysbiosis and microbial byproducts, in the onset of PD is also discussed. We have highlighted the landmark discoveries in the field of PD particularly focusing on the gut-brain axis. A better comprehension of the interaction between the gut-brain axis, gut microbiota, and PD can usher in novel therapeutic and diagnostic approaches. [ABSTRACT FROM AUTHOR]

Recent research in the field of electrochemical biosensors equipped with peptides and nanomaterials have been categorized, reviewed, and critically analyzed. Indeed, using these innovative biosensors can revolutionize biomedical diagnostics in the future. Saving lives, time, and money in this field will be considered as some main benefits of this type of diagnosis. Here, these biosensors have been categorized and evaluated in four main sections. In the first section, the focus is on investigating the types of electrochemical peptide-based nanobiosensors applied to detect pathogenic microorganisms, microbial toxins, and viruses. In the second section, due to the importance of rapid diagnosis and prognosis of various cancers, the electrochemical peptide-based nanobiosensors designed to detect cancer biomarkers have been reviewed and analyzed. In the third section, the electrochemical peptide-based nanobiosensors, which were applied to detect the essential and effective biomolecules in the various diseases, and health control, including enzymes, hormones, biomarkers, and other biomolecules, have been considered. Finally, using a comprehensive analysis, all the used elements in these biosensors have been presented as conceptual diagrams that can effectively guide researchers in future developments. The essential factors in evaluating and analyzing these electrochemical peptide-based nanobiosensors such as analyte, peptide sequence, functional groups interacted between the peptide sequences and other biosensing components, the applied nanomaterials, diagnostic techniques, detection range, and limit of detection have also been included. Other analyzable items such as the type of used redox marker and the location of the peptide sequence against the signal transducer were also considered. [ABSTRACT FROM AUTHOR]

Foodborne pathogens and microbial toxins are the main causes of foodborne illness. However, trace pathogens and toxins in foods are difficult to detect. Thus, techniques for their rapid and sensitive identification and quantification are urgently needed. Phages can specifically recognize and adhere to certain species of microbes or toxins due to molecular complementation between capsid proteins of phages and receptors on the host cell wall or toxins, and thus they have been successfully developed into a detection platform for pathogens and toxins. This review presents an update on phage‐based luminescent detection technologies as well as their working principles and characteristics. Based on phage display techniques of temperate phages, reporter gene detection assays have been designed to sensitively detect trace pathogens by luminous intensity. By the host‐specific lytic effects of virulent phages, enzyme‐catalyzed chemiluminescent detection technologies for pathogens have been exploited. Notably, these phage‐based luminescent detection technologies can discriminate viable versus dead microbes. Further, highly selective and sensitive immune‐based assays have been developed to detect trace toxins qualitatively and quantitatively via antibody analogs displayed by phages, such as phage‐ELISA (enzyme‐linked immunosorbent assay) and phage‐IPCR (immuno‐polymerase chain reaction). This literature research may lead to novel and innocuous phage‐based rapid detection technologies to ensure food safety. [ABSTRACT FROM AUTHOR]

Having an insight into graphene and graphene derivatives such as graphene oxide, reduced graphene oxide and graphene quantum dots is necessary since it can help scientists to detect possible properties and features that could be useful when using these carbon materials in preparation of a nanocomposites. In recent years, graphene and its derivatives have attracted a lot of attention and been extensively applied in biosensors due to fascinating properties, such as large surface area, optical and magnetic properties, and high elasticity for the detection of microorganisms as they can be modified with some other materials such as macromolecules, oxide metals and metals to improve the electrochemical behaviour of the biosensor. In this review paper, biosensor design strategies based on graphene and its derivatives (graphene-based nanocomposites in biosensors) are described. Then their application for the detection of microorganisms including prions, viroids, viral and bacterial cells as well as fungi, protozoa, microbial toxins and even microbial sources of antibiotics is reviewed. [ABSTRACT FROM AUTHOR]

A growing body of evidence has underscored the role of horizontal gene transfer (HGT) in animal evolution. Previously, we discovered the horizontal transfer of the gene encoding the eukaryotic genotoxin cytolethal distending toxin B (cdtB) from the pea aphid Acyrthosiphon pisum secondary endosymbiont (APSE) phages to drosophilid and aphid nuclear genomes. Here, we report cdtB in the nuclear genome of the gall-forming "swede midge" Contarinia nasturtii (Diptera: Cecidomyiidae) via HGT. We searched all available gall midge genome sequences for evidence of APSE-to-insect HGT events and found five toxin genes (aip56 , cdtB , lysozyme , rhs , and sltxB) transferred horizontally to cecidomyiid nuclear genomes. Surprisingly, phylogenetic analyses of HGT candidates indicated APSE phages were often not the ancestral donor lineage of the toxin gene to cecidomyiids. We used a phylogenetic signal statistic to test a transfer-by-proximity hypothesis for animal HGT, which suggested that microbe-to-insect HGT was more likely between taxa that share environments than those from different environments. Many of the toxins we found in midge genomes target eukaryotic cells, and catalytic residues important for toxin function are conserved in insect copies. This class of horizontally transferred, eukaryotic cell-targeting genes is potentially important in insect adaptation. [ABSTRACT FROM AUTHOR]

A previous study showed that classical building‐related symptoms (BRS) were related to indoor dust and microbial toxicity via boar sperm motility assay, a sensitive method for measuring mitochondrial toxicity. In this cross‐sectional study, we analyzed whether teachers' most common work‐related non‐literature‐known BRS (nBRS) were also associated with dust or microbial toxicity. Teachers from 15 schools in Finland completed a questionnaire evaluating 20 nBRS including general, eye, respiratory, hearing, sleep, and mental symptoms. Boar sperm motility assay was used to measure the toxicity of extracts from wiped dust and microbial fallout samples collected from teachers' classrooms. 231 teachers answered a questionnaire and their classroom toxicity data were recorded. A negative binomial mixed model showed that teachers' work‐related nBRS were 2.9‐fold (95% CI: 1.2‐7.3) higher in classrooms with highly toxic dust samples compared to classrooms with non‐toxic dust samples (p = 0.024). The RR of work‐related nBRS was 1.8 (95% CI: 1.1‐2.9) for toxic microbial samples (p = 0.022). Teachers' BRS appeared to be broader than reported in the literature, and the work‐related nBRS were associated with toxic dusts and microbes in classrooms. [ABSTRACT FROM AUTHOR]