Epigallocatechin Gallate Alleviates Staphylococcal Enterotoxin A-Induced Intestinal Barrier Damage by Regulating Gut Microbiota and Inhibiting the TLR4-NF-κB/MAPKs-NLRP3 Inflammatory Cascade.

Natural phytochemicals have attracted increasing attention because of their promising ability to tackle bacteriotoxin-induced public safety concerns. However, it is unclear how natural phytochemicals regulate the intestinal barrier dysfunction caused by bacteriotoxin, such as staphylococcal enterotoxin A (SEA). This study aims to illustrate the in vitro and in vivo protective mechanism of epigallocatechin gallate (EGCG) on SEA-triggered intestinal barrier damage and inflammation. Results show that EGCG alleviates intestinal barrier damage by effectively inhibiting SEA-induced intestinal permeability increase, tight junction protein and mucin loss, and intestinal cell apoptosis. EGCG also reduces intestinal inflammation by suppressing the TLR4-NF-κB/MAPKs-NLRP3 pathway. Importantly, EGCG reverses gut microbiota dysbiosis and short-chain fatty acid (SCFA) content decrease induced by SEA. It is worth noting that this study also detects the direct interaction between the phytochemical and virulence factors and finds that EGCG effectively not only inhibits the secretion of SEA but also binds with the secreted SEA to attenuate its toxicity. Taken together, EGCG mitigates SEA-induced intestinal barrier dysfunction via gut microbiota SCFA-mediated TLR4-NF-κB/MAPKs-NLRP3 inflammatory cascade inhibition. Overall, this research provides enlightening insight into the application of bacteriotoxin-targeting natural compounds in the field of food safety and human wellness.

Staphylococcal enterotoxin A induces DNA damage in hepatocytes and liver tissues.

Staphylococcal enterotoxin A (SEA) is a foodborne bacterial toxin that can cause food poisoning, but little research has been done on the DNA damage caused by SEA. The aim of this research was to investigate the action of SEA in inducing DNA damage and oxidative stress response in hepatocytes and liver tissues. After treating HL-7702 and BRL-3A cells with different concentrations of SEA (0, 300, 600 ng/mL and 0, 400, 800 ng/mL), the production of phosphorylated H2AX (γH2AX) and p53 binding protein 1 (53BP1) aggregates was detected by confocal fluorescence microscopy, and the increases in ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), p53 protein expression were assessed by Western blot analysis, while increased reactive oxygen species (ROS) content was confirmed by flow cytometry and fluorescence probe. The genotoxicity of SEA to cells was attenuated after the addition of an oxidative inhibitor, demonstrating that SEA induced intracellular DNA damage through the oxidative pathway and a dose-dependent relationship was observed between the oxidation index and SEA. These experimental results deepen our understanding of SEA damage to cells at the genetic level, and provide a new orientation for the prevention and cure of food borne diseases caused by Staphylococcal enterotoxins (SEs).

Hazard of Staphylococcal Enterotoxins in Food and Promising Strategies for Natural Products against Virulence.

Staphylococcal enterotoxins (SEs) secreted by Staphylococcus aureus frequently contaminate food and cause serious foodborne diseases but are ignored during food processing and even cold-chain storage. Notably, SEs are stable and resistant to harsh sterilization environments, which can induce more serious hazards to public health than the bacterium itself. Therefore, it is necessary to develop promising strategies to control SE contamination in food and improve food safety. Natural products not only have various pharmaceutical properties, such as antimicrobial and antitoxin activities, but they are also eco-friendly, safe, nutritive, and barely drug-resistant. Here, the hazards of SEs and the promising natural compounds with different inhibitory mechanisms are summarized and classified. The key points of future research and applications for natural products against bacterial toxin contamination in food are also prospected. Overall, this review may provide enlightening insights for screening effective natural compounds to prevent foodborne diseases caused by bacterial toxins.

Staphylococcal Enterotoxin A Induces Intestinal Barrier Dysfunction and Activates NLRP3 Inflammasome via NF-κB/MAPK Signaling Pathways in Mice.

Staphylococcal enterotoxin A (SEA), the toxin protein secreted by Staphylococcus aureus, can cause staphylococcal food poisoning outbreaks and seriously threaten global public health. However, little is known about the pathogenesis of SEA in staphylococcal foodborne diseases. In this study, the effect of SEA on intestinal barrier injury and NLRP3 inflammasome activation was investigated by exposing BALB/c mice to SEA with increasing doses and a potential toxic mechanism was elucidated. Our findings suggested that SEA exposure provoked villi injury and suppressed the expression of ZO-1 and occludin proteins, thereby inducing intestinal barrier dysfunction and small intestinal injury in mice. Concurrently, SEA significantly up-regulated the expression of NLRP3 inflammasome-associated proteins and triggered the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in jejunum tissues. Notably, selective inhibitors of MAPKs and NF-κB p65 ameliorated the activation of NLRP3 inflammasome stimulated by SEA, which further indicated that SEA could activate NLRP3 inflammasome through NF-κB/MAPK pathways. In summary, SEA was first confirmed to induce intestinal barrier dysfunction and activate NLRP3 inflammasome via NF-κB/MAPK signaling pathways. These findings will contribute to a more comprehensive understanding of the pathogenesis of SEA and related drug-screening for the treatment and prevention of bacteriotoxin-caused foodborne diseases via targeting specific pathways.