Search Results (45,123)

Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer’s disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly Porphyromonas gingivalis, has garnered significant attention. P. gingivalis, a major driver of periodontitis, is recognized for its potential systemic effects and its putative role in AD pathogenesis. This review examines evidence connecting P. gingivalis to hallmark AD features, such as amyloid β accumulation, tau hyperphosphorylation, neuroinflammation, and other neuropathological features consistent with AD. Virulence factors, such as gingipains and lipopolysaccharides, were shown to be implicated in blood–brain barrier disruption, neuroinflammation, and neuronal damage. P. gingivalis-derived outer membrane vesicles may serve to disseminate virulence factors to brain tissues. Indirect mechanisms, including systemic inflammation triggered by chronic periodontal infections, are also supposed to exacerbate neurodegenerative processes. While the exact pathways remain uncertain, studies detecting P. gingivalis virulence factors and its other components in AD-affected brains support their possible role in disease pathogenesis. This review underscores the need for further investigation into P. gingivalis-mediated mechanisms and their interplay with host responses. Understanding these interactions could provide critical insights into novel strategies for reducing AD risk through periodontal disease management. Full article

Metabolic disorders, including type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome, are systemic conditions that profoundly impact the skin microbiota, a dynamic community of bacteria, fungi, viruses, and mites essential for cutaneous health. Dysbiosis caused by metabolic dysfunction contributes to skin barrier disruption, immune dysregulation, and increased susceptibility to inflammatory skin diseases, including psoriasis, atopic dermatitis, and acne. For instance, hyperglycemia in T2DM leads to the formation of advanced glycation end products (AGEs), which bind to the receptor for AGEs (RAGE) on keratinocytes and immune cells, promoting oxidative stress and inflammation while facilitating Staphylococcus aureus colonization in atopic dermatitis. Similarly, obesity-induced dysregulation of sebaceous lipid composition increases saturated fatty acids, favoring pathogenic strains of Cutibacterium acnes, which produce inflammatory metabolites that exacerbate acne. Advances in metabolomics and microbiome sequencing have unveiled critical biomarkers, such as short-chain fatty acids and microbial signatures, predictive of therapeutic outcomes. For example, elevated butyrate levels in psoriasis have been associated with reduced Th17-mediated inflammation, while the presence of specific Lactobacillus strains has shown potential to modulate immune tolerance in atopic dermatitis. Furthermore, machine learning models are increasingly used to integrate multi-omics data, enabling personalized interventions. Emerging therapies, such as probiotics and postbiotics, aim to restore microbial diversity, while phage therapy selectively targets pathogenic bacteria like Staphylococcus aureus without disrupting beneficial flora. Clinical trials have demonstrated significant reductions in inflammatory lesions and improved quality-of-life metrics in patients receiving these microbiota-targeted treatments. This review synthesizes current evidence on the bidirectional interplay between metabolic disorders and skin microbiota, highlighting therapeutic implications and future directions. By addressing systemic metabolic dysfunction and microbiota-mediated pathways, precision strategies are paving the way for improved patient outcomes in dermatologic care. Full article

Background/Objectives: This study aimed to develop gel nanoemulsions (NEs) of Brazilian essential oils (EOs) from Eugenia uniflora and Psidium guajava, as well as to perform chemical characterization and investigate the antimicrobial activity of the EOs and NEs. Results/Conclusions: The main chemical compounds of E. uniflora EO were curzerene (34.80%) and germacrene B (11.92%), while those of P. guajava EO were β-caryophyllene (25.92%), β-selinene (22.64%), and γ-selinene (19.13%). The NEs of E. uniflora and P. guajava had droplet sizes of 105.30 and 99.50 nm and polydispersity index (PDI) values of 0.32 and 0.43, respectively. The NEs remained stable for 30 days of storage at 25 °C, with droplet sizes of 104.7 and 103.8 nm, PDI values below 0.50, and no phase separation. The NE of E. uniflora exhibited inhibition zones ranging from 8.41 to 15.13 mm against the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Additionally, the NE of E. uniflora showed the largest inhibition zones against Candida albicans (20.97 mm) and Candida krusei (15.20 mm), along with low minimum inhibitory concentration (MIC) values (0.54–1.22 mg/mL) and minimal bactericidal concentration (MBC) values (4.84–11.02 mg/mL) against these pathogenic yeasts. The NE of P. guajava demonstrated low MIC (1.26 mg/mL) and MBC (11.35 mg/mL) values for C. krusei. The time–growth inhibition assay also suggests the effectiveness of the NE against the tested pathogens S. aureus and E. coli, highlighting its potential as a novel alternative therapeutic agent. Full article

The emergence of colistin-resistant Enterobacteriaceae in food products is a growing concern due to the potential transfer of resistance to human pathogens. This study aimed to assess the prevalence of colistin-resistant Enterobacteriaceae in raw and ready-to-eat food samples collected from two regions of Italy (Apulia and Basilicata) and to evaluate their resistance phenotypes and genetic characteristics. A total of 1000 food samples were screened, with a prevalence of 4.4% of colistin-resistant Enterobacteriaceae. The majority of the isolates belonged to Enterobacter spp. (60%), followed by Moellerella wisconsensis, Atlantibacter hermannii, Klebsiella pneumoniae, and Escherichia coli, among others. Genomic sequencing and antimicrobial susceptibility testing revealed high levels of resistance to β-lactams, with most isolates exhibiting multidrug resistance (MDR). Notably, seven isolates harbored mcr genes (mcr-1, mcr-9, and mcr-10). Additionally, in four of them were predicted the IncHI2 plasmids, known to facilitate the spread of colistin resistance. Furthermore, 56 antimicrobial resistance genes were identified, suggesting the genetic mechanisms underlying resistance to several antibiotic classes. Virulence gene analysis showed that E. coli and other isolates carried genes linked to pathogenicity, increasing the potential risk to public health. This study emphasizes the role of food as a potential reservoir for colistin-resistant bacteria and the importance of monitoring the spread of AMR genes in foodborne pathogens. Full article

(1) Background: In recent years, the increasing emergence of multidrug-resistant pathogens in pig farms has begun to pose a severe threat to animal welfare and, by extension, public health. In this study, we aimed to explore the biological characteristics and genomic features of bacteriophages that are capable of lysing porcine multidrug-resistant E. coli, which was isolated from sewage. In doing so, we provided a reference for phage therapies that can be used to treat multidrug-resistant strains. (2) Method: Using the multidrug-resistant E. coli isolate sq-1 as the host bacterium, bacteriophages were isolated and purified from fecal samples using a double-layer agar plate method. The morphology was observed using a transmission electron microscope, and its host range, optimal multiplicity of infection (MOI), one-step growth curve, thermal stability, acid–base tolerance, and in vitro antibacterial ability were tested. Genomic features were analyzed using whole-genome sequencing. (3) Results: A lytic phage named vB_EcoS_Psq-1 (abbreviated as Psq-1) was successfully isolated. Electron microscopy revealed that Psq-1 belongs to the family of long-tailed phages, possessing clear and transparent plaques of approximately 1 mm in diameter. Psq-1 only lyses the host bacterium and does not affect other E. coli strains or other species of bacteria. The optimal MOI for phage Psq-1 was 0.1, with a latent period of 25 min, an exponential growth period of 25 min, and a lysis yield of 44.21 PFU/cell. Its activity remains stable at temperatures between 40 °C and 60 °C and from pH 4.0 to pH 13.0. Psq-1 exhibited a significant inhibitory effect on E. coli in liquid culture medium. The nucleic acid type of phage Psq-1 was dsDNA, with a total genome length of 44,183 bp and a GC content of 52.16%. No known resistance, lysogenic, or virulence-related genes were detected. The whole genome contains 55 open reading frames (ORFs). (4) Conclusions: This study isolated a bacteriophage that is capable of lysing multidrug-resistant E. coli. Characterized by a narrow E. coli lysis range, a long latent period, limited lytic ability, and stable biological properties, this bacteriophage can serve as a reference isolate for E. coli phages and can provide biological materials and data to support research on bacteriophages that are effective against multidrug-resistant porcine E. coli. Full article

Due to an increased demand for natural food additives, clove oil was assessed as a natural alternative to chemical disinfectants in produce washing. This study assessed the antimicrobial activity of 5 and 10% (v/v) clove oil-amended wash liquid (CO) using a zone of inhibition (ZIB) test and determined the time required to completely inactivate pathogenic bacteria using bacterial death curve analysis. A washing experiment was used to evaluate CO’s ability to inhibit bacterial growth on inoculated RTE spinach and in the wash water. The findings showed that Shigella flexneri, Salmonella Typhimurium, and Salmonella enterica recovery were completely inhibited within 5 min. Escherichia coli and Staphylococcus aureus recovery were completely inhibited at 10 and 30 min, respectively. The ZIB test showed that 5% CO had the highest inhibitory effect on both Salmonella strains and E. coli with approximately 10 mm ZIB diameter. Additionally, 5% CO completely inactivated all bacterial strains on spinach samples and in the wash water except for S. aureus. A total of 80 mg/L peracetic acid (PAA) resulted in >2log CFU/mL recovery on experimental washed samples. These findings suggest that 5% CO was highly effective in inhibiting microbial growth on RTE spinach, potentially contributing to sustainable food safety and shelf-life extension strategies. Full article

Influenza A viruses (IAVs) are highly contagious pathogens that cause zoonotic disease with limited availability of antiviral therapies, presenting ongoing challenges to both public health and the livestock industry. Unveiling host proteins that are crucial to the IAV life cycle can help clarify mechanisms of viral replication and identify potential targets for developing alternative host-directed therapies. Using a four-dimensional (4D), label-free methodology coupled with bioinformatics analysis, we analyzed the expression patterns of cellular proteins that changed following H9N2 virus infection. Compared to the control group, the H9N2 infected group displayed 732 differentially expressed proteins (DEPs), with 298 proteins showing upregulation and 434 proteins showing downregulation. Gene Ontology (GO) functional analysis showed that DEPs were catalog in 11 biological processes, three cellular components, and eight molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEPs were involved in processes including cytokine signaling pathways induced by virus infection and protein digestion and absorption. Proteins including TP53, DDX58, and STAT3 were among the top hub proteins in the protein–protein interaction (PPI) analysis, suggesting that these signaling cascades could be essential for the propagation of IAVs. Furthermore, the host protein SNAPIN was chosen to ascertain the accuracy of expression changes identified through a proteomic analysis. The results indicated that SNAPIN was downregulated following infection with IAVs both in vitro and in vivo, which is consistent with the proteomics results, suggesting that SNAPIN may serve as a key regulatory factor in the viral life cycle of IAVs. Our research delineates an extensive interaction map of IAV infection within the A549 cells, facilitating the discovery of pivotal proteins that contribute to the virus’s propagation, potentially offering target candidates to screen for antiviral therapeutics. Full article

The discovery and application of bacteriocin-producing probiotics, such as Streptococcus salivarius K12 (BLIS K12), represent significant advances in the prevention and management of bacterial infections, particularly in the oral cavity and upper respiratory tract. Originally developed for its bacteriocin-mediated inhibition of the important bacterial pathogen Streptococcus pyogenes, BLIS K12 has more recently also demonstrated potential in the modulation and prevention of viral infections, including COVID-19. Emerging evidence also suggests a broader role for BLIS K12 in immune regulation, with implications for controlling hyperinflammatory responses and enhancing mucosal immunity. Of particular interest is recent work indicating that BLIS K12 can modulate antibody responses against viral antigens, such as the SARS-CoV-2 spike protein, positioning it as a unique adjunct in managing viral infections. This review chronicles the pathway of BLIS K12’s probiotic development, emphasizing its relevant bacteriocin mechanisms, oral health applications, emerging antiviral properties, and potential broader health benefits through immune modulation, all of which position it as a significant non-pharmacological adjunct in managing respiratory and immune health Full article

Lactobacillus is a key genus of probiotics commonly utilized for the treatment of oral infections The primary aim of our research was to investigate the probiotic potential of the newly isolated Levilactobacillus brevis DPL5 strain from human breast milk, focusing on its ability to combat biofilm-forming pathogens such as Staphylococcus aureus. Employing in vitro approaches, we demonstrate L. brevis DPL5′s ability to endure at pH 3 with survival rates above 30%, and withstand the osmotic stress often found during industrial processes like fermentation and freeze drying, retaining over 90% viability. The lyophilized cell-free supernatant of L. brevis DPL5 had a significant antagonistic effect against biofilm-producing nasal strains of Staphylococcus aureus, and it completely eradicated biofilms at subinhibitory concentrations of 20 mg·mL⁻¹. Higher concentrations of 69 mg·mL⁻¹ were found to have a 99% bactericidal effect, based on the conducted probability analysis, indicating the production of bactericidal bioactive extracellular compounds capable of disrupting the biofilm formation of pathogens like S. aureus. Furthermore, genome-wide sequencing and analysis of L. brevis DPL5 with cutting-edge Nanopore technology has uncovered over 50 genes linked to probiotic activity, supporting its ability to adapt and thrive in the harsh gut environment. The genome also contains multiple biosynthetic gene clusters such as lanthipeptide class IV, Type III polyketide synthase (T3PKS), and ribosomally synthesized, and post-translationally modified peptides (RiPP-like compounds), all of which are associated with antibacterial properties. Our study paves the way for the further exploration of DPL5, setting the stage for innovative, nature-inspired solutions to combat stubborn bacterial infections. Full article

Metagenomics analysis has enabled the measurement of the microbiome diversity in environmental samples without prior targeted enrichment. Functional and phylogenetic studies based on microbial diversity retrieved using HTS platforms have advanced from detecting known organisms and discovering unknown species to applications in disease diagnostics. Robust validation processes are essential for test reliability, requiring standard samples and databases deriving from real samples and in silico generated artificial controls. We propose a MeStanG as a resource for generating HTS Nanopore data sets to evaluate present and emerging bioinformatics pipelines. MeStanG allows samples to be designed with user-defined organism abundances expressed as number of reads, reference sequences, and predetermined or custom errors by sequencing profiles. The simulator pipeline was evaluated by analyzing its output mock metagenomic samples containing known read abundances using read mapping, genome assembly, and taxonomic classification on three scenarios: a bacterial community composed of nine different organisms, samples resembling pathogen-infected wheat plants, and a viral pathogen serial dilution sampling. The evaluation was able to report consistently the same organisms, and their read abundances as provided in the mock metagenomic sample design. Based on this performance and its novel capacity of generating exact number of reads, MeStanG can be used by scientists to develop mock metagenomic samples (artificial HTS data sets) to assess the diagnostic performance metrics of bioinformatic pipelines, allowing the user to choose predetermined or customized models for research and training. Full article

Among the various causes of rhomboencephalitis, Listeria monocytogenes infection is the most common. However, conventional microbiological methods often yield negative results, making diagnosis challenging and leading to extensive, often inconclusive, diagnostics. Advanced molecular techniques like metagenomic next-generation sequencing (mNGS) offer a powerful and efficient approach to pathogen identification. We present a case of life-threatening rhomboencephalitis in a 32-year-old immunocompetent patient where extensive microbiological, immunological, and biochemical tests were inconclusive. Given the patient’s consumption of unpasteurized homemade cheese, neurolisteriosis was suspected, and mNGS was employed on clinical samples (CSF, serum, urine) and the food source to identify the pathogen. mNGS detected L. monocytogenes in both patient samples and the cheese. Mapping reads were distributed across the genome, with 18.9% coverage in clinical samples and 11.8% in the cheese sample. Additionally, the Listeriolysin (hlyA) gene was detected with 22.3% coverage in clinical samples and 12.3% in the food source, confirming neurolisteriosis. The patient fully recovered following antibiotic treatment. This case underscores the importance of mNGS in diagnosing CNS infections when conventional methods yield negative results, and supports its inclusion in diagnostic protocols for suspected neurolisteriosis, particularly when traditional methods prove inadequate. Full article

Previously, we assessed the pathogenicity of eleven endemic entomopathogenic fungi (EPF), including six Beauveria isolates, four Metarhizium isolates, and one M. pingshaense, against the agricultural pest Spodoptera frugiperda (fall armyworm, FAW). We found that four Beauveria and one Metarhizium isolates were effective, with Beauveria isolates B-0571 and B-1311 exhibiting high mortality within 24 h post-spore application. This study aimed to identify and characterise the entomopathogenesis mechanisms of these isolates as potential FAW biocontrol agents. All Beauveria isolates were determined as B. bassiana, the Metarhizium isolates as two M. robertsii, one M. majus, and an unknown Metarhizium species. Despite the high mortality from B-0571 and B-1311 isolates, scanning electron microscopy showed no fungal spore germination on dead larvae 24 h after spore application. Four insecticide compound gene clusters, i.e., bassianolide, beauvericin, beauveriolide, and oosporein, were identified and characterised in all B. bassiana isolates. These compounds are hypothesised to contribute to the high early mortality rates in FAWs. Identifying and characterising gene clusters encoding these insecticide compounds in B-0571 and B-1311 will contribute to a better understanding of the entomopathogenicity of these isolates that will be vital to developing these EPF isolates as sustainable alternative FAW biocontrol agents. Full article

Alternaria panax, the primary pathogen that causes ginseng Alternaria leaf blight disease, can lead to a 20–30% reduction in ginseng yield. WD40 repeat-containing proteins are evolutionarily conserved proteins with diverse functions between different organisms. In this study, we characterized the roles of a WD40 repeat-containing protein in A. panax. The deletion of ApWD40a impaired the mycelial growth, reduced the sporulation, and significantly decreased the efficiency in utilizing various carbon sources. The ΔApwd40a mutant showed increased sensitivity to osmotic stress and metal ion stress induced by sorbitol, NaCl, and KCl, but decreased the sensitivity to a cell wall stress factor (SDS) and oxidative stress factors (paraquat and H₂O₂). Pathogenicity assays performed on detached ginseng leaves and roots revealed that the disruption of ApWD40a significantly decreased the fungal virulence through attenuating melanin and mycotoxin production by A. panax. A comparative transcriptome analysis revealed that ApWD40a was involved in many metabolic and biosynthetic processes, including amino acid metabolism, carbon metabolism, sulfate metabolic pathways, and secondary metabolite pathways. In particular, a significantly upregulated gene that encoded a sulfate permease 2 protein in ΔApwd40a, named ApSulP2, was deleted in the wild-type strain of A. panax. The deletion of ApSulP2 resulted in reduced biomass under sulfate-free conditions, demonstrating that the sulfate transport was impaired. Taken together, our findings highlight that ApWD40a played crucial roles in different biological processes and the pathogenicity of A. panax through modulating the expressions of genes involved in various primary and secondary metabolic processes. Full article

SARS-CoV-2 continues to be a major global health threat. In this study, we performed a comprehensive meta-analysis on the epitopes of SARS-CoV-2, revealing its immunological landscape. Furthermore, using Shannon entropy for sequence conservation analysis and structural network-based methods identified candidate epitopes that are highly conserved and evolutionarily constrained in SARS-CoV-2 and other zoonotic coronaviruses. Finally, the population coverage of T cell epitopes was analyzed. The results highlighted regions within each SARS-CoV-2 protein where the immunological activity of antibodies, CD4⁺, and CD8⁺ T cell responses was predominantly concentrated. Sequence-based correlation analysis found that epitopes recognized by B cells and CD4⁺ T cells showed a positive correlation with high viral variability, and these high variability regions were typically linked to robust immune responses. Conversely, epitopes recognized by CD8⁺ T cells exhibited a negative correlation with high variability. From a structural network degree perspective, no clear correlation was identified between B cell antibody epitopes and CD4⁺ T cell reactivity with the degree of residue network connectivity. However, a significant positive correlation was observed between CD8⁺ T cell reactivity and the degree of residue network connectivity. By integrating sequence Shannon entropy and structural network correlation analysis, we pinpointed highly conserved and evolutionarily constrained SARS-CoV-2 candidate epitopes. Furthermore, we utilized immunoinformatics to assess the conservation of SARS-CoV-2 within coronaviruses and the population coverage of these epitopes. Our analysis uncovered key immune responses linked to preventing viral infection and viral clearance, emphasized areas of interest for broad-spectrum SARS-CoV-2 vaccine development, and offered insights for future research and clinical applications. Full article

Equine herpesvirus-1 (EHV-1) is a significant pathogen that causes substantial economic losses in the equine industry worldwide, which leads to severe respiratory diseases and abortions in horses. However, reports of EHV-1 infection in donkeys are limited, particularly in China. This case study reported an EHV-1-induced respiratory disease in Dezhou donkey foals in Shandong Province, China, in July 2024. Three one-month-old foals exhibited high fever, nasal discharge, and respiratory distress, with a 100% mortality rate. The causative agent, strain LC126, was isolated from a one-month-old donkey foal exhibiting severe respiratory disease. Phylogenetic analysis of the EHV-1 isolate LC126 showed close similarity to EHV-1. Overall, our study revealed that EHV-1 can cause respiratory distress as well as death in donkeys. The study underscores the emerging threat of EHV-1 in donkeys and highlights the need for veterinarians and breeders to give proper attention to the potential threat of EHV-1 outbreaks. Full article