Pulmonary tuberculosis in humans is characterised by features of immunopathology, which influence both antimycobacterial therapy and the long-term prognosis. In the blood of tuberculosis patients, immunopathology manifests itself in reduced immune responses to mitogenic substances. Previous studies have demonstrated the influence of tuberculosis serum on T-cell and monocyte function, but the exact mechanisms remain unclear. Here, we performed a case/control study to analyse the influence of tuberculosis serum milieu changes on (i) T-cell stimulation (using Staphylococcal Enterotoxin B), (ii) monocyte stimulation (using the Toll-like receptor agonist Pam3CSK4), (iii) T-cell/monocyte interaction characterised by the response against the lectin phytohemagglutinin, by using a novel peripheral blood mononuclear cell invitro assay. Cell-specific activation marker and cytokine expression were determined by multicolor flow cytometry. Staphylococcal Enterotoxin B mainly induced cytokine expression by T cells, while Pam3CSK4 stimulated monocytes to secrete distinct cytokine signatures. Phytohemagglutinin induced activation and cytokine expression in both T cells and monocytes. Notably, tuberculosis patient serum samples affected exclusively phytohemagglutinin stimulated T-cell responses and particularly activation marker as well as CD40L/IL-2 positive CD4+ T-cell subsets were decreased as compared to serum from healthy contacts. Neither Staphylococcal Enterotoxin B-mediated T-cell stimulation nor phytohemagglutinin or Pam3CSK4 induced monocyte cytokines (i.e., Interleukin-6, Interleukin-8, Tumour Necrosis Factor-α) were affected by the tuberculosis patients' serum samples. These results highlight the immunosuppressive influence of the tuberculosis serum milieu, which specifically reduced T-cell responses to phytohemagglutinin, probably through impaired function of the accessory monocytes required for stimulation.

Skin barrier dysfunction is central to inflammation and susceptibility to infection in atopic dermatitis (AD). Cutaneous T-cell lymphoma (CTCL) shares clinical similarities with AD and is also associated with a high prevalence of Staphylococcus aureus (S. aureus) colonisation. However, the mechanisms driving skin barrier damage in CTCL and the contribution of bacteria remain poorly understood. We investigate how the interplay between S. aureus (and staphylococcal enterotoxins (SEs)) and primary malignant- and non-malignant T cells affects keratinocyte expression of skin barrier proteins; invitro, in an EL4 murine lymphoma model of bacteria-driven tumour progression, and in CTCL patient lesions colonised with SE-producing S. aureus before and after bacterial eradication by antibiotic treatment. S. aureus and SEs activate malignant and non-malignant T cells to release barrier-repressing cytokines, including IL-4, IL-13, IL-22, and OSM, and JAK-dependent downregulation of filaggrin and loricrin in keratinocytes. In the EL4 model, bacteria-colonised tumour-bearing mice show significant filaggrin loss in tumour-adjacent epidermis, whereas antibiotic-treated mice maintain near-normal expression. Clinically, antibiotic eradication of SE-producing S. aureus partially restores filaggrin and loricrin expression in three of four patients, paralleling reduced inflammatory signalling. SE-producing S. aureus promotes skin barrier impairment in CTCL through cytokine-driven, JAK-dependent repression of structural proteins in keratinocytes. These findings identify microbial-immune crosstalk as a contributor to CTCL skin pathology and provide mechanistic rationale for strategies targeting S. aureus colonisation as adjunctive therapy in CTCL.

Staphylococcal enterotoxin A (SEA) is a major foodborne pathogen toxin capable of causing severe food poisoning even at nanogram levels. However, as widely reported, accurate quantification of SEA in complex food matrices remains challenging due to matrix effects from coexisting proteins, lipids, carbohydrates, and reducing small molecules. Herein, we report an innovative anti-interference photoelectrochemical (PEC) immunosensing platform constructed from a hydrogen-substituted graphdiyne (HsGDY)/Cu2O photocathode further functionalized with a dendritic peptide tetramer (DPT) bearing four terminal peptide chains. The HsGDY layer, with its extended π-conjugated framework and porous structure, stabilizes the Cu2O component and broadens light absorption, thereby enhancing charge separation and photocurrent generation. Meanwhile, DPT forms a multivalent interfacial layer that suppresses nonspecific adsorption, minimizing matrix interference and ensuring high specificity. SEA antibodies immobilized on the HsGDY/Cu2O photocathode mediate highly specific antigen recognition. The HsGDY-enhanced photocurrent, combined with the DPT-mediated suppression of nonspecific adsorption, yields exceptional sensitivity, selectivity, and interference tolerance. The platform exhibits a wide linear range of 0.05-5000 ng/mL and a low detection limit of 18.63 pg/mL. This strategy offers a general approach for developing high-performance, anti-interference PEC immunosensors applicable to food safety monitoring, clinical diagnostics, and environmental analysis.

Single-dose mSEB-mi3 nanoparticle vaccine elicits robust humoral immunity and protects mice against SEB intoxication and MRSA infection.

Electrospinning of gelatin-based composite Nanofibrous coating loaded with Citral and its antibacterial application in chilled meat preservation.

Notch signaling pathway modulates immune function by regulating T cell development, differentiation, and function. Previous studies from our group have demonstrated that maternal exposure to staphylococcal enterotoxin B (SEB) during pregnancy alters T cell frequencies in offspring. To further investigate the underlying mechanisms, we examined the impact of prenatal SEB exposure on the Notch signaling pathway, a critical regulator of thymic T cell maturation. In this study, pregnant rats were injected with 15 μg SEB on gestational day 16. Thymus tissues were aseptically collected from 14-day-old and 3-month-old offspring in both the PBS and SEB-exposed groups. The expression of Notch pathway components-including receptors, ligands, and downstream target genes-was assessed using real-time PCR and western blot. It was found that prenatal SEB exposure significantly downregulated mRNA and protein levels of Notch receptors and target genes in thymic T lymphocytes in neonatal offspring. Additionally, ligand expression was reduced in thymic stromal cells. Strikingly, this suppression was reversed in adulthood, with SEB-exposed offspring exhibiting elevated expression of Notch receptors, ligands, and target genes. These results indicate that prenatal SEB exposure transiently inhibits Notch signaling in neonatal thymocytes but leads to a compensatory upregulation in adulthood. This biphasic modulation suggests that prenatal SEB exposure can induce long-term, dynamic reprogramming of thymic Notch signaling, with potential implications for T cell-mediated immunity across developmental stages.

Synergistic antibody neutralization of SEB is driven by allosteric transfer entropy.

Chronic rhinosinusitis (CRS), a common upper respiratory disease, has been closely linked to Staphylococcus aureus and its enterotoxin superantigens. However, the specific mechanisms by which staphylococcal enterotoxin superantigens contribute to CRS pathophysiology remain unclear. To investigate the association between staphylococcal enterotoxin superantigen activity and CRS. A case-control epidemiological study was conducted from February 2022 to February 2024 at Northern Jiangsu People’s Hospital. Seventy-eight patients with CRS constituted the case group, and 78 patients undergoing septum surgery served as controls. CRS cases were further divided into CRS without nasal polyps (n = 42) and CRS with nasal polyps (CRSwNP, n = 36). Nasal tissue homogenates were analyzed by enzyme-linked immunosorbent assay to measure anti-SEA, anti-SEB, anti-SEC, anti-SED, and anti-SEE IgE levels. Histopathological examination of nasal polyps was performed using hematoxylin–eosin staining. Statistical analyses included the t-test or Mann–Whitney U test for group comparisons, with P < .05 considered statistically significant. Anti-SEA, anti-SEB, anti-SEC, anti-SED, and anti-SEE IgE levels were significantly higher in the observation group (2190.23 (120.47), 1722.29 (115.39), 1983.16 (103.16), 2120.14 (132.44), and 1955.17 (112.56) ng/mL, respectively) compared with controls (245.45 (67.28), 293.10 (87.03), 323.13 (121.34), 283.11 (91.13), and 302.11 (88.24) ng/mL; all P < .05). Within CRS subgroups, anti-SEB IgE was markedly higher in CRSwNP (2833.32 (167.07) ng/mL) than in CRS without nasal polyps (1862.26 (98.09) ng/mL; P < .05). Of the 36 CRSwNP cases, 8 were eosinophilic and 28 non-eosinophilic. Elevated IgE antibodies against SEA, SEB, SEC, SED, and SEE may contribute to CRS onset and progression, with anti-SEB IgE showing a particularly strong link to nasal polyp development.

Staphylococcal enterotoxins (SEs) belong to a family of highly potent superantigens produced by Staphylococcus aureus and play a significant role in food poisoning and toxic shock syndrome. Among the SE family type B (SEB) is unique as it is involved in naturally occurring diseases and also has a history of military use as an incapacitating agent. Thus, the accurate detection of SEs and particularly SEB is critical. However, immuno-based detection methods encounter intrinsic difficulties due to S. aureus' co-production of staphylococcal protein A (SpA), which has a strong affinity for immunoglobulins. This interaction can result in false-positive results in antibody-based assays, thereby complicating the interpretation of results with regard to presence and quantity of SEB. Commercially available detection methods seek to address this issue through SpA depletion by pre-incubating samples with animal serum. While these approaches mitigate the impact of SpA interference, they frequently result in diminished assay sensitivity. In this study, a previously established highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for SEB detection was optimised to maintain its low detection limit in the one-digit pg/mL-range while simultaneously abolishing its reactivity to SpA in S. aureus liquid-culture supernatants. The modifications were focused on direct alterations to existing detection antibodies by a) adapting the immunoglobulin subclass and generation of antibody fragments through recombinant technology, and b) the careful selection of control capture antibodies. This study can be taken as a blueprint for optimised ELISA strategies to overcome SpA related false results while maintaining high sensitivity for SE detection and quantification.

Staphylococcal enterotoxin B (SEB) is a major pathogenic factor in foodborne diseases, and its rapid and sensitive detection is crucial for early warning of food safety risks and public health protection. In this study, a colorimetric immunosensing system for SEB detection was constructed based on a magnetic covalent organic framework (COF) composite loaded with platinum nanoparticles (Pt NPs) that exhibit dual enzymatic activities. The effective loading of Pt NPs endows the composite with excellent peroxidase (POD) and oxidase (OXD)-like activities. The COF matrix not only provides abundant binding sites for Pt NP dispersion but also enhances substrate adsorption, thereby significantly improving catalytic efficiency. By introducing an Fe3O4 core, the nanocomposite enables facile preparation of antibody-nanoparticle conjugates through separation and enrichment functions. The Fe3O4@COF@Pt nanocomposite demonstrates excellent peroxidase- and oxidase-like activities, capable of decomposing H2O2 and O2 to generate hydroxyl radicals (˙OH) and superoxide anions (O2˙-), which catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidized TMB (OXTMB), resulting in a visible color change for signal output. The sensor achieves specific detection by utilizing its peroxidase-mimicking activity, exhibiting a linear detection range of 1-200 ng mL-1 with a detection limit as low as 0.395 ng mL-1. This nanozyme-linked immunosorbent assay (NLISA) based on Fe3O4@COF@Pt offers a highly sensitive and convenient platform for SEB detection.

Staphylococcus aureus is a leading cause of foodborne diarrhea, primarily due to staphylococcal enterotoxins (SEs). This study employed whole‐genome sequencing to characterize 106 S. aureus isolates from diarrheal patients in East China (2019–2024). We identified 23 sequence types, with ST398 (22.6%) and ST5 (7.5%) among the most prevalent. Clonal complex analysis revealed the codominance of CC398 and CC5 (22.6% each), with CC5 exhibiting higher virulence and antimicrobial resistance (AMR) gene diversity. A significant 18.9% of isolates were methicillin‐resistant S. aureus (MRSA). While the tetracycline resistance gene tet38 was ubiquitous, 23.6% of isolates were multidrug‐resistant. Plasmid profiling showed rep16 (53.8%) and rep5a (51.9%) as the most common replicons. Crucially, SEs were detected in 51.9% of isolates, with a high prevalence in CC5 (83.3%) and a complete absence in CC398. A key temporal trend was the decline in virulence factors, coinciding with the rise of CC398. These findings reveal a dynamic genomic landscape and underscore the need for continued surveillance of diarrheagenic S. aureus .

Staphylococcus species include both well-known pathogens andoverlooked reservoirs of antimicrobial resistance. With rising resistance ratesand limited treatment options, especially for methicillin-resistant strains,interest in alternative therapies has resurged. Among them, bacteriophages(phages) are promising biological agents due to their high specificity, lowtoxicity, ability to disrupt biofilms, and co-evolution with bacterial hosts.This review explores the biology, pan-genomics, diversity, and therapeuticrelevance of staphylococcal phages. We revisit their historical discovery andre-emergence as tools against multidrug-resistant infections, highlightingmorphological features, replication strategies, and recent taxonomic updates.Genomic analyses reveal distinct clusters of genome sizes, rare presence ofresistance genes, and implications of transduction, bacterial defense systems,and phage-encoded anti-defense mechanisms. Preclinical studies show broad hostrange and synergistic activity with diverse antimicrobial agents, whileengineered phage enzymes expand therapeutic possibilities. Clinical evidence,though limited, supports safety and efficacy in compassionate-use cases andearly trials targeting Staphylococcus. Finally, we examinebusiness models translating phage innovation into applied therapies, emphasizingregulatory, logistical, and financial challenges. In this broader context, phagetechnologies are not just alternatives to antibiotics-they represent anopportunity for innovation in global health. Their full potential depends oncoordinated actions across science, industry, and policy.

Otitis media (OM) is an infection frequently involving multiple bacterial species. Staphylococcus aureus and Pseudomonas aeruginosa are key pathogens in community and healthcare-associated cases. Precisely identifying these bacteria and their virulence factors is essential for public health. This research used molecular methods to detect specific virulence genes in S. aureus and P. aeruginosa obtained from OM patients in Basra, Iraq. Among 96 patient samples, 24 S. aureus and 20 P. aeruginosa isolates were confirmed using culture, biochemical tests, and the Vitek-2 system. DNA from these isolates was analyzed with multiplex-PCR to target the S. aureus genes for staphylococcal enterotoxins A (sea) and B (seb), toxic shock syndrome toxin (tst-1), and exfoliative toxin A (eta). Detection rates were (62.5%) for sea, (41.7%) for seb, (54.2%) for tst-1, and (8.3%) for eta. For P. aeruginosa, the exotoxin A gene (exoA) was found in (80%) of isolates. This study demonstrates a high occurrence of these crucial toxin genes in local OM isolates, underscoring their likely contribution to disease development.

In this study, a total of 400 samples were collected from the milk, skin, vaginal mucosa, and nasal mucosa of 50 lactating Hair goats and 50 lactating Saanen goats raised in the Aydın province during the summer of 2010. The samples were transported to the laboratory of the Department of Microbiology, Faculty of Veterinary Medicine, Adnan Menderes University. Staphylococcus aureus was isolated from 48 samples (12%). Polymerase chain reaction (PCR) analysis revealed that 13 (27%) of these isolates harbored the sek staphylococcal enterotoxin gene (278-bp fragment). Among the detected enterotoxin genes, 10 (66.7%) were obtained from milk isolates, 2 (22%) from nasal isolates, and 1 (11.1%) from a skin isolate. Distribution by breed showed that 8 (42.1%) of the genes were detected in milk isolates of Hair goats, 2 (25%) in milk isolates of Saanen goats, 1 (5.2%) in a skin isolate of a Hair goat, and 2 (10.5%) in nasal isolates of Hair goats. The higher prevalence of S. aureus in Hair goats may be associated with their extensive breeding practices and increased environmental exposure to the pathogen. These findings emphasize the importance of management, nutrition, and hygiene practices in Hair goat flocks. Furthermore, molecular methods provided rapid and highly sensitive detection of staphylococcal enterotoxin genes.

Staphylococcal enterotoxins (SEs) are key virulence factors in staphylococcal food poisoning (SFP). This study aimed to assess the frequency of staphylococcal enterotoxin genes among isolates from food handlers in Iran. Nasal swabs were collected from 575 food handlers. PCR using specific primers was used to detect sea, seb, and sec genes as markers for SEA, SEB, and SEC enterotoxins. Out of 575 nasal swabs, 168 (29.2%) were positive for S. aureus. Overall, 63.1% (106/168) of S. aureus isolates among food handlers were positive for the presence of at least one or more SE genes. Of the 168 isolates, sea, seb, and sec genes were found in 57 (33.9%), 29 (17.2%), and 20 (11.9%) isolates, respectively. A significant percentage of Iranian food handlers carry enterotoxigenic S. aureus in their noses. Therefore, strict hygiene measures, screening programs, and control of these carriers are necessary to prevent food contamination with S. aureus during food handling.

Platelet concentrates (PCs) are used to treat patients with platelet deficiencies. PCs are stored at 20–24 °C under agitation for up to 7 days to maintain platelet functionality, but these conditions are amenable for proliferation of contaminants such as Staphylococcus aureus, posing a risk for transfusion-transmitted infections. We investigated the contribution of staphylococcal enterotoxins (SEs) type G (SEG) and type H (SEH) to platelet activation, cytokine release, microRNA (miRNA) modulation, and in vivo virulence. PCs were inoculated with wildtype S. aureus CBS2016-05 or SE-deficient mutants (Δseg, Δseh, ΔΔsegh) and monitored during storage. Flow cytometry revealed progressive elevation of platelet activation markers CD62P and Annexin V in contaminated PCs, with significantly higher expression in wildtype compared to SE-mutant strains. Cytokine profiling demonstrated that SEs modulate pro- and anti-inflammatory mediators, notably CCL2, TGF-β1, IFN-γ, and TNF-α, implicating SEG in their regulation. Next-generation sequencing and RT-qPCR validation identified transient induction of immune-related microRNAs miR-98-5p, miR-146a-5p, miR-221-3p, miR-320a-3p, with SE-dependent expression patterns. In a silkworm infection model, wildtype S. aureus-contaminated PCs exhibited significantly higher lethality than SE-deficient strains, confirming toxin-mediated virulence. Collectively, these findings reveal that SEs exacerbate platelet activation and immune dysregulation during storage, enhancing bacterial pathogenicity. This study identifies platelet-derived cytokine and miRNA signatures as potential biomarkers of bacterial contamination and underscores the need to mitigate SE-driven platelet dysfunction to improve transfusion safety.

Exposure to microgravity decreases bone volume and increases marrow fat, partly due to impaired BMSC osteogenesis and enhanced adipogenesis. Staphylococcal enterotoxin C2 (SEC2) can influence BMSC differentiation, potentially promoting osteogenesis. This study investigated SEC2’s effects on bone loss and marrow fat in hindlimb suspension (HLS) mice and BMSC differentiation under simulated microgravity. Results showed SEC2 alleviated bone deterioration and reduced marrow adiposity, promoting osteogenic over adipogenic differentiation by activating ERK/β-catenin signaling pathways. SEC2 increased ERK phosphorylation and β-catenin nuclear translocation, with effects diminished upon β-catenin knockdown. These findings reveal a novel mechanism by which SEC2 modulates BMSC fate under microgravity, highlighting its potential as a therapeutic agent for preventing bone loss and marrow adiposity in microgravity conditions.

Staphylococcal enterotoxins (SEs), particularly enterotoxin C (SEC), are potent superantigens primarily known for causing food poisoning, but recent studies have highlighted their potential role in immune-mediated intestinal diseases. Despite the widespread use of food preservatives, their influence on SEC production—especially from coagulase-negative staphylococci (CNS)—remains poorly understood. In this study, we evaluated the effects of commonly used preservatives, including sodium chloride, potassium nitrate, and sorbic acid, on the expression and production of SEC3 and SECepi in Staphylococcus aureus and S. epidermidis, respectively. Using ELISA and RT-qPCR, we analyzed toxin levels at both the protein and mRNA levels. Proliferation assays on human PBMCs assessed the mitogenic potential of culture supernatants. While sodium chloride and potassium nitrate did not significantly alter SEC levels or bacterial growth, only sorbic acid at 0.07% consistently inhibited both mRNA expression and protein production of SEC3 and SECepi. Furthermore, supernatants from sorbic acid-treated cultures induced significantly lower PBMC proliferation. These results suggest that even sub-emetic concentrations of enterotoxins may have immunomodulatory effects, and sorbic acid could be a promising agent in mitigating such risks.

Staphylococcal enterotoxins in cancer immunotherapy: An overview of translational advances and targeting strategies.

ABSTRACTStaphylococcal enterotoxins (SE) crosslink the MHC‐II on antigen‐presenting cells (APC) with the T‐cell receptor, inducing a polyclonal T‐cell response. Although APCs are the initial targets of SE and are critical in shaping subsequent T‐cell activation, the effects of SE on APC function remain poorly understood. This study investigates the immunomodulatory effects of staphylococcal enterotoxin A (SEA) on monocytes and their differentiation into monocyte‐derived dendritic cells (moDC) or macrophages (MDM). Transcriptomic analyses of human monocytes via RNA sequencing revealed SEA‐induced enrichment of gene pathways associated with inflammation, infection, and dermatitis, effects that were amplified in the presence of T cells. Phenotypic and functional characterization showed that SEA‐primed monocytes differentiated into MDM with an altered polarization, deviating from classical M1/M2 pathways. SEA‐primed MDM exhibited downregulation of key markers, including HLA‐DR, CD80, CD86, and PD‐L1. Functional assays demonstrated that SEA‐primed MDM pushed hyperinflammatory T‐cell responses, with significantly enhanced proliferation and IFN‐γ secretion. In contrast, following SEA‐priming, moDC retained robust antigen‐presenting capabilities and displayed enhanced expression of molecules involved in T‐cell interactions. These findings provide mechanistic insights into SEA‐mediated immune modulation, illustrating how SEA reprograms MDM functions and amplifies proinflammatory T‐cell responses. This advances our understanding of superantigen‐driven immune interactions, offering a foundation for developing therapeutic strategies to mitigate superantigen‐mediated immune conditions.