Search Results (709)

Background: Foodborne pathogenic Escherichia coli is a major public health concern due to its frequent association with meat and meat products and its potential to harbor virulence factors and antimicrobial resistance (AMR) determinants. Objective: This study aimed to investigate the prevalence, virulence gene profiles, and AMR patterns of E. coli isolates obtained from beef and chicken meat products. Methods: A total of 200 beef and chicken meat product samples were collected from retail markets in Samsun, Türkiye. Isolation of E. coli was performed using conventional culture-based methods, and PCR targeting the uspA gene was used for molecular confirmation. The presence of virulence genes (stx1, stx2, eae, and hlyA) was investigated by PCR. Antimicrobial susceptibility testing was conducted using the disk diffusion method, and multidrug resistance (MDR) and multiple antibiotic resistance (MAR) indices were evaluated. Results: Among the 200 samples analyzed, 80 (40%) were positive for E. coli, including 38 (38%) beef and 42 (42%) chicken meat samples. A total of 185 E. coli isolates were recovered and confirmed by PCR. Virulence gene analysis showed that stx2 was the most prevalent gene (51.4%), followed by eae (37.3%), hlyA (13.0%), and stx1 (6.5%). Antimicrobial susceptibility testing demonstrated high resistance rates to tetracycline (69.7%), ampicillin (58.4%), trimethoprim–sulfamethoxazole (48.1%), streptomycin (40.5%), nalidixic acid (40.0%), chloramphenicol (40.0%), and ciprofloxacin (34.1%). In contrast, the lowest resistance rates were observed for imipenem (2.2%), amoxicillin–clavulanate (4.9%), and amikacin (7.6%). Moreover, 126 isolates (68.1%) were identified as MDR, exhibiting resistance to at least three antimicrobial agents. The MAR index ranged from 0.06 to 1.00. Conclusions: The coexistence of virulence-associated genes and high AMR rates among E. coli isolates from meat products indicates a potential public health risk. These findings highlight the importance of continuous monitoring of pathogenic and antimicrobial-resistant E. coli throughout the food production chain. Full article

Diabetes mellitus comprises a group of heterogeneous metabolic disorders characterized by persistent hyperglycemia, progressive β-cell dysfunction, and multi-organ complications. Although type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have distinct pathogenic origins, both involve immune dysregulation, tissue stress, release of danger signals, and chronic inflammation. Dendritic cells (DCs), as antigen-presenting cells, integrate innate immune sensing, antigen presentation, cytokine production, T-cell regulation, and peripheral immune tolerance, placing them at a critical interface between autoimmunity and metabolic inflammation. In T1DM, DCs contribute to β-cell autoantigen presentation, tolerance breakdown, autoreactive T-cell activation, and insulitis amplification. In T2DM, DCs may contribute to adipose tissue inflammation, hepatic immunometabolic crosstalk, β-cell stress, vascular inflammation, and immune remodeling associated with diabetes-related complications. Here, we review the disease-specific roles of DC subsets in T1DM and T2DM and discuss shared molecular mechanisms, including pattern-recognition receptor signaling, metabolic reprogramming, inflammasome activation, cytokine networks, and the shift from immune tolerance to inflammation. We also evaluate therapeutic DC reprogramming strategies and their potential implications for targeted immunometabolic intervention in diabetes. Full article

Sexually transmitted infections remain a major public health concern among men who have sex with men (MSM), particularly due to the high frequency of coinfections and the limitations of syndromic management. This study aimed to describe the frequency of bacterial sexually transmitted and urogenital pathogens among symptomatic MSM attending two specialized sexual health clinics in Mexico City. A prospective cross-sectional study was conducted with 150 adult MSM presenting symptoms suggestive of urethritis. Urethral swab samples were analyzed using a multiplex real-time polymerase chain reaction (PCR) assay for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum, and Trichomonas vaginalis. At least one pathogen was detected in 91/150 participants (60.7%). N. gonorrhoeae was the most frequent pathogen (33.3%), followed by U. urealyticum (15.3%), M. genitalium (9.3%), and C. trachomatis (9.3%). Coinfections were identified in 15 participants, representing 10.0% of the total population and 16.5% of those with a positive PCR result. Most coinfections involved N. gonorrhoeae, particularly with C. trachomatis. These findings provide descriptive microbiological evidence on the frequency and coinfection patterns of bacterial sexually transmitted infections (STIs) associated pathogens among symptomatic MSM attending specialized sexual health clinics in Mexico City. The high detection rate and occurrence of concurrent infections highlight the limitations of syndromic management and support the value of timely multiplex molecular diagnostics to improve etiological characterization, antimicrobial stewardship, and clinical decision-making in this population. Full article

Honey bees (Apis mellifera) are key pollinators in agricultural ecosystems that face increasing pressure from pathogens and environmental change. However, how these environmental factors interact remains incompletely understood. To assess associations between climate, landscape composition, and pathogen occurrence in real agroecosystems, we monitored honey bee colonies across 30 apiaries in southern Italy over two years, in summer and autumn. Molecular screening revealed widespread multi-pathogen exposure, with two viruses, Black Queen Cell Virus (BQCV) and Deformed Wing Virus (DWV), and gut trypanosomatid parasite (Lotmaria passim) being the most frequently detected. In contrast, Nosema ceranae, along with Bee Macula-like Virus (BeeMLV) and Acute Bee Paralysis Virus (ABPV), occurred at lower but still notable frequencies. Infections were generally more frequent in adult foragers than in in-hive bees and larvae, and overall pathogen occurrence tended to be higher in summer than in autumn. Higher humidity was associated with higher overall pathogen occurrence and coinfection levels, whereas higher temperature showed a weaker association with these outcomes. Associations between landscape composition and pathogen occurrence differed across pathogens: a higher proportion of semi-natural habitats was associated with lower viral occurrence, particularly BQCV and DWV; however, N. ceranae was more frequently detected under the same landscape conditions. In contrast, L. passim showed context-dependent responses, with landscape effects emerging only through interactions with humidity and temperature. Pathogen coinfections were more occurrent under warm, humid conditions, although this pattern was partially buffered in landscapes richer in semi-natural habitats. Together, these results indicate that, within the studied apiaries, honey bee pathogen occurrence was associated with climate, season, and land use. These findings suggest that environmental context should be considered when interpreting honey bee health monitoring data in heterogeneous agricultural landscapes, with potential implications for apiary management. Full article

Canine distemper virus (CDV), currently classified within the species Morbillivirus canis, is a major vaccine-preventable pathogen of domestic dogs and a wide range of susceptible wildlife species. Still, laboratory-confirmed epidemiological data from Portugal remain scarce. This retrospective study investigated CDV molecular detection in 637 diagnostic samples from dogs with clinical suspicion of canine distemper, received from 190 veterinary medical centres across Portugal between 2013 and 2025. Cerebrospinal fluid, EDTA-anticoagulated whole blood, rectal swabs, and conjunctival swabs were tested for CDV RNA using a reverse transcription real-time PCR (RT-qPCR) assay in a qualitative approach. Overall, 215 submissions were CDV RT-qPCR-positive, corresponding to a positivity of 33.8% (95% confidence interval: 30.2–37.5%). Positivity was not significantly associated with sex, age, or Nomenclature of Territorial Units for Statistics level 2 (NUTS 2) region, but differed significantly according to specimen type, with the highest detection observed in EDTA-anticoagulated whole blood and conjunctival swabs. Mixed-breed dogs were over-represented among submitted samples and positive cases, probably reflecting management, exposure, and vaccination-related factors rather than intrinsic breed susceptibility. The central finding was a pronounced post-2020 decline in CDV RT-qPCR positivity, with very low or absent annual detection between 2021 and 2025. This pattern indicates reduced molecular detection within a passive diagnostic population but should not be interpreted as evidence of national elimination. Continued vaccination and strengthened surveillance at the domestic dog–wildlife interface remain essential. Full article

Virus infection requires coordinated activation of pathogen-sensing, innate immune, and cellular stress response pathways to mount an effective antiviral defense. Recognition of nucleic acid pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) initiates signaling cascades that drive the production of type I interferons (IFNs) and proinflammatory cytokines. These responses are often accompanied by the activation of integrated stress response pathways that help optimize host defense. Cytosolic double-stranded dsDNA, generated during viral infection or released from damaged mitochondria, is sensed by cyclic GMP-AMP synthase (cGAS), which generates 2′3′-cGAMP to activate stimulator of interferon genes (STING). Activated STING translocates from the endoplasmic reticulum to the Golgi, where it drives TBK1-dependent IFN and cytokine production. Previous reports show that cGAS activity is enhanced by Ras-GAP SH3 domain binding protein 1 (G3BP1), a key nucleator of stress granules (SGs), independent of its role in SG assembly. Here, we identify a non-canonical role of G3BP1 as a regulator of DNA sensing responses at multiple levels, including STING intracellular trafficking, in addition to potentiating cGAS activity. Loss of G3BP1 impaired STING-dependent IFN and cytokine responses to HSV-1 infection and viral DNA. G3BP1-deficient cells showed reduced cGAMP-induced STING translocation to the Golgi, induction of type I IFN and proinflammatory cytokines, and activation of the ER stress kinase PERK and stress granule formation. Together, these findings demonstrate G3BP1-STING as a node linking DNA sensing, innate immunity, and stress signaling with broad implications for antiviral defense and diseases characterized by aberrant DNA sensing and stress responses, including neurodegeneration, fibrosis, and autoimmunity. Full article

Extracellular vesicles (EVs) are key mediators of intercellular communication across biological kingdoms, with central roles in immune regulation and disease processes. Despite shared structural features, EVs derived from bacteria, plants, and mammalian cells differ substantially in their biogenesis, molecular composition, and immunological functions. EV formation pathways generate vesicles with distinct cargo profiles, including pathogen-associated molecular patterns (PAMPs) in bacterial EVs, regulatory small RNAs in plant-derived vesicles, and cytokines, microRNAs, and antigen-presenting complexes in mammalian EVs. Differences in cargo result in divergent immune outcomes. Bacterial EVs predominantly activate innate immunity via pattern recognition receptors such as Toll-like receptors, whereas plant-derived EVs exhibit low immunogenicity and mediate cross-kingdom RNA interference. In contrast, mammalian EVs primarily regulate immune responses by modulating antigen presentation and cytokine signaling. These findings support a framework in which EV origin determines immunological function and therapeutic applicability. This perspective highlights the importance of selecting appropriate EV sources for vaccine development, regenerative medicine, and targeted delivery strategies, while addressing current challenges related to heterogeneity, standardization, and safety. Full article

The innate immune response is a critical defense mechanism by which vertebrates recognize and eliminate invading pathogens. Pattern recognition receptors (PRRs) detect pathogen-associated molecular patterns and activate downstream signaling pathways. NOD1, a classic PRR of the NLR family, recruits the adaptor protein RIPK2 to initiate antibacterial signaling. In this study, we cloned and characterized the NOD1 gene from snakehead (Channa argus). Briefly, the full-length NOD1 cDNA is 2829 bp encoding 943 amino acids, showing high homology with Perciformes. The qPCR analysis revealed widespread NOD1 gene expression in various tissues, with significant upregulation in the gill (p < 0.05) and spleen (p < 0.05) following bacterial infection. Overexpression of the NOD1 gene activated the NF-κB signaling pathway in a dose- and time-dependent manner, and specifically responded to the bacterial ligand iE-DAP but not to other tested ligands. Furthermore, NOD1 synergized with the downstream adaptor RIPK2 to enhance NF-κB activity, and direct protein interaction between NOD1 and RIPK2 was confirmed by co-immunoprecipitation. Taken together, these findings demonstrate that snakehead NOD1 plays a critical role in the host antimicrobial immune response. Full article

The first line of defense against infection is provided by the innate immune system, which is able to recognize molecular patterns in a variety of infectious agents through the action of different families of pattern recognition receptors (PRRs). These effectors detect the invading agent and trigger powerful inflammatory responses that help fight the infection from the very beginning. However, inflammatory reactions can be damaging for the host and must be properly controlled to prevent pathological consequences. Here we provide a comprehensive review of the important role of autophagy, a catabolic pathway that degrades cellular components for quality control and regulatory purposes, in the regulation of innate immune responses, and the underlying mechanisms involved. Inflammatory pathways discussed in this review include those triggered by Toll-like receptors (TLRs), Retinoic acid-Inducible Gene (RIG)-I-like receptors (RLRs), Nucleotide-binding Oligomerization Domain (NOD)-like receptors (NLRs), and the receptor for cyclic GMP–AMP Stimulator of Interferon Genes (STING). Finally, we also consider examples where autophagy plays context-dependent or even pro-inflammatory roles, reflecting a complex involvement that remains to be fully characterized. Full article

Banana Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), poses a significant threat to global banana production; however, effective and sustainable control strategies remain limited. Extracellular self-DNA (esDNA), which functions as a damage-associated molecular pattern (DAMP), has recently been identified as a crucial regulator of plant innate immunity. Nonetheless, it is unclear whether the immune regulatory function of esDNA varies with disease progression. In this study, we examined the effects of esDNA derived from banana leaves exhibiting different disease severities on plant resistance to Fusarium wilt. Hydroponic experiments revealed that esDNA displayed a distinct disease-stage-dependent regulatory pattern. EsDNA from mildly diseased tissues significantly suppressed Foc TR4 colonization, supported plant growth, and mitigated oxidative damage, whereas esDNA from severely dise ased tissues lost protective effects and even intensified cellular stress. Physiological analyses indicated that beneficial esDNA effectively reduced H₂O₂ and malondialdehyde accumulation while enhancing antioxidant enzyme activities and phenylpropanoid metabolism. Transcriptome profiling further demonstrated that esDNA extensively altered pathogen-induced gene expression, with enrichment of pathways involved in metabolic and redox homeostasis. These transcriptional changes correlate with the observed reduction in oxidative damage and improved plant growth, suggesting that restoration of homeostasis may contribute to esDNA-mediated resistance. Our findings collectively demonstrate that esDNA serves as a dynamic DAMP signal, exhibiting effects that depend on the disease stage. This study offers new insights into the role of plant self-DNA in mediating immunity and presents a promising strategy for developing environmentally sustainable control measures against banana Fusarium wilt. Full article

Sepsis-associated encephalopathy (SAE) is a frequent neurological complication of sepsis, driven by six interconnected pathophysiological components: (1) systemic inflammation-triggered neuroinflammatory cascades, initiated by systemic recognition of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and propagated by pro-inflammatory mediators; (2) central nervous system (CNS) immune cell-mediated neuroinflammation, wherein microglia, regulatory T cells, and neutrophils dynamically regulate inflammatory progression; (3) blood–brain barrier (BBB) disruption, progressing from functional disturbance to structural damage via tight junction degradation and immune infiltration; (4) multimodal programmed cell death, encompassing autophagy, apoptosis, pyroptosis, and ferroptosis driven by mitochondrial dysfunction; (5) neurotransmitter network imbalance, manifesting as cholinergic deficiency and glutamate excitotoxicity; and (6) gut–brain axis dysregulation, characterized by reduced microbiota-derived metabolites such as butyrate and indolepropionic acid. These components are organized along a core pathological axis comprising four sequential stages: neuroinflammatory storm (encompassing components 1 and 2) → BBB disruption and microcirculatory disturbances (component 3) → multimodal programmed cell death (component 4) → neurotransmitter imbalance (component 5), with the gut–brain axis (component 6) functioning as a bidirectional regulatory node that intersects and modulates all four stages. Mitochondrial dysfunction serves as the central converging node linking these pathological axes. Targeted interventions against neuroinflammation, immune cell modulation, BBB restoration, inhibition of aberrant cell death, neurotransmitter homeostasis, and gut microbiota remodeling hold therapeutic promise. Elucidating the crosstalk among these pathways will accelerate the clinical translation of precision therapies for SAE. Full article

The Yangtze sturgeon (Acipenser dabryanus), a critically endangered living fossil whose wild populations are now extinct, faces new challenges to survival in captive breeding. Among these, the emergence of albino and gray color morphs raise fundamental questions about the molecular basis and physiological consequences of pigmentation loss. Here, we integrated histological, transcriptomic, and quantitative PCR to investigate pigmentation variation and associated immune alterations in this species. Histology revealed a complete absence of melanin in albino individuals and marked reduction in gray morphs. Transcriptomic profiling across the three color morphs uncovered a broad downregulation of core melanogenic genes, including PMEL, TYR, TYRP1, DCT, SLC45A2, OCA2, MREG, and MLPH, indicating impaired melanosome formation, melanin synthesis, and intracellular transport. Notably, pigmentation loss coincided with systematic changes in the expression of immune-related genes: phagosome pathway genes (e.g., C3, MHC I/II, TAP2) were downregulated, while pro-inflammatory mediators (e.g., IL-8, IL-17, CXCL10) were upregulated, suggesting a transcriptional pattern correlated with reduced expression of pathogen defense-related genes and increased genes associated with inflammation mediators. These findings reveal a mechanistic correlation between melanin deficiency and immune dysfunction in a basal vertebrate lineage, offering the first molecular evidence of an association between albinism and altered immune-related gene expression in sturgeons and highlighting its implications for conservation and captive management. Full article

The development of pathogen-associated molecular patterns (PAMPs) that signal via pathogen recognition receptors (PRRs) on innate immune cells is a strategy that is widely adopted in adjuvant research. Less well studied is how covalently linking different PAMPs affects the immune response. Herein, we summarise the research on the effect of PAMP linkage on innate and adaptive immune responses. These covalently linked or “chimeric” PAMPs often lead to immune cell synergies that are greater than those exhibited by the admixed (unconjugated) PAMPs, with several PAMP conjugates exhibiting remarkable adjuvant activity in a variety of disease contexts that include infectious disease, allergy, and cancer immunotherapy. This improvement in immune cell activation is thought to be due to more effective crosstalk between the different PRR signalling pathways, as conjugation ensures that each cell receives each class of PAMP. In addition, PAMP conjugates can form particulates, which has been postulated to lead to improved adjuvanticity, or they may facilitate the targeting of endosomal PRRs via the PRR-mediated endocytosis of the alternative PAMP in the conjugate. PAMP conjugates can also reduce the toxicity of individual PAMPs. However, not all PAMP conjugates are effective, and there are still many aspects of this research platform that are poorly understood, including how linker chemistry affects the immune response and how PRR signalling pathways or PAMP combinations combine to skew the immune response. We will address these and other outstanding questions that relate to the use of PAMP conjugates as vaccine adjuvants. Full article

Introduction: Stenotrophomonas maltophilia (S. maltophilia) has emerged as an important opportunistic pathogen. It is resistant to most available antibiotics due to its intrinsic resistance, leaving only some antibacterial agents as possible therapeutic options, which is further complicated by acquired mechanisms of antimicrobial resistance. This study aimed to provide a comprehensive genomic characterization of clinical S. maltophilia complex (Smc) isolates, focusing on molecular characterization of its resistance and virulence, since studies tackling this are scarce in Oman. Methods: This study is a prospective cross-sectional study, in which a total of 21 clinical isolates of Smc were collected from different clinical samples and further characterized using Whole Genome Sequencing. Results: Besides S. maltophilia, the isolates included S. hibiscicola, S. pavanii, and S. muris for the first time in Oman. All isolates were found to be susceptible to cefiderocol, levofloxacin, and minocycline. Sequence types (STs) were diverse among the isolates, with more than half of the isolates showing new STs with novel alleles. Additionally, blaOXA-2, sul1, and the recently described aac(6′)-Iap and aph(9)-Ic were detected among the isolates. Moreover, virulence-associated genes (smf-1, pilT, pilQ, gpmA, rmlA, spgM, stmPr1, plcN, clpP, and katE) were highly conserved across all isolates. Mobile genetic elements were detected in most of the isolates (76.20%). Conclusions: The collected isolates showed high ST diversity and showed no specific pattern in terms of antibiotic susceptibility and resistance genes. More studies are needed to establish relationships between the different members of the Smc and the different molecular resistome and virulome. Full article

The purpose of this study was to use data mining and network pharmacology to determine drug patterns for bovine viral diarrhea (BVD). The frequency, properties, tastes, meridian tropism, and functions of prescription data were gathered and examined from four literature databases (2004–2024). Cluster analysis was used to find prescription patterns, and the Apriori algorithm (SPSS Modeler 18) was used to find associations. A total of 391 literature-derived prescription records were included in the analysis, involving 189 distinct herbal medicines and a cumulative herb-use frequency of 2031 occurrences. These herbs primarily enter the liver meridian and were categorized as cold, warm, or neutral. The predominant tastes were bitter, pungent, and sweet. Five frequently recorded herbs and 14 co-occurrence patterns among herbs were extracted. According to traditional Chinese medicine (TCM), spleen–stomach deficiencies and damp-heat pathogens are linked to BVD. These medication patterns were mainly associated with heat-clearing, detoxification, spleen-strengthening, and Qi-regulating strategies in TCVM theory. Targets were screened, PPI networks were constructed, and enrichment studies for core herbs (Baitouweng, Huangbo, Huangqin, Qinpi, and Zhizi) were performed using network pharmacology. The binding affinities between disease targets and active components were further assessed using molecular docking. The findings provide a descriptive summary of medication patterns and generate preliminary hypotheses regarding potential compound–target–pathway associations involved in the symptomatic and supportive use of TCM for BVD. Full article