Influences of dissolved organic matters on the adsorption and bioavailability of sulfadiazine: Molecular weight- and type-dependent heterogeneities.

The bioavailability of contaminants in aquatic environments was highly related with the existing forms (soluble or adsorbed) and properties of dissolved organic matters (DOMs). In this study, the molecular weight (MWs)-dependent effects of DOMs on the adsorption and bioavailability of sulfadiazine were explored. Colloid ZnO and Al2O3 were employed as the representative colloidal particles, and algae-derived organic matter (AOM) and humic acid (HA) were selected as typical autochthonous and allochthonous DOMs. The ultrafiltration procedure was applied to divide the bulk DOMs into high MW (HMW-, 1 kDã0.45 µm) and low MW (LMW-, <1 kDa) fractions. Results showed that HMW-DOM contained more aromatic and protein-like substances as compared to the LMW counterparts. In addition, presence of AOM promoted sulfadiazine adsorption capabilities by 1.19-4.54 folds and mitigated the inhibition ratio by 0.56-0.78 folds, whereas those of HA inhibited sulfadiazine adsorption by 0.27-0.84 folds and enhanced the biotoxicity by 1.21-1.45 folds. Regardless of different DOM types, HMW-fraction exhibited highest effects on sulfadiazine adsorption and bioavailability, followed by the bulk- and LMW-fractions. Two-dimensional correlation spectroscopy showed that sulfadiazine was adsorbed on colloidal surfaces prior to AOM, and the subsequent adsorption of AOM can provide additional sites for sulfadiazine adsorption, which decreased the concentrations of aqueous sulfadiazine as well as the biotoxicity to Microcystis aeruginosa (M. aeruginosa). The HA, however, was preferentially adsorbed on colloidal surfaces, which hindered the subsequent sulfadiazine adsorption and resulted in a high sulfadiazine abundance in aqueous solution as well as the enhanced biotoxicity to M. aeruginosa. This study highlighted the importance of the types and MWs of DOMs in influencing the behaviors and ecological effects of aquatic contaminants.

Dissolved organic matter promoted hydroxyl radical formation and phenanthrene attenuation during oxygenation of iron-pillared montmorillonites.

The oxygenation of Fe(II)-bearing minerals for hydroxyl radicals (HO•) formation and contaminant attenuation receives increasing attentions. However, information on dissolved organic matter (DOM) with different types, concentrations, and molecular weights (MWs) in manipulating HO• formation and contaminant attenuation during mineral oxygenation remain unclear. In this study, four iron-pillared montmorillonites (IPMs) and two DOM samples [e.g., humic acids (HA) and fulvic acids (FA)] were prepared to explore the HO• formation and phenanthrene attenuation during the oxygenation of IPMs in the presence or absence of DOMs. Results showed that iron-pillared and high-temperature calcination procedures extended the interlayer domain of IPMs, which provided favorable conditions for a high HO• production from 1293 to 14537 µmol kg-1. The surface-absorbed/low crystalline Fe(Ⅱ) was the predominant Fe(Ⅱ) fractionations for HO• production, and presence of DOMs significantly enhanced the HO• production and phenanthrene attenuation. Moreover, regardless of the types and concentrations, the low MW (LMW, <1 kDa) fraction within DOM pool contributed highest to HO• production and phenanthrene attenuation, followed by the bulk and high MW (HMW-, 1 kDa∼0.45 µm) fractions, and FA exhibited more efficient effects in promoting HO• production and phenanthrene attenuation than HA. The fluorescent spectral analysis further revealed that phenolic-like fluorophores in LMW-fraction were the main substances responsible for the enhanced HO• production and phenanthrene attenuation. The results deepen our understandings toward the behaviors and fate of aquatic HO• and contaminants, and also provide technical guidance for the remediation of contaminated environments.

Synthesis and antibacterial evaluation of novel psoralen derivatives against methicillin-resistant Staphylococcus aureus (MRSA).

Today, the bacterial infections caused by multidrug-resistant pathogens seriously threaten human health. Thereby, there is an urgent need to discover antibacterial drugs with novel mechanism. Here, novel psoralen derivatives had been designed and synthesized by a scaffold hopping strategy. Among these targeted twenty-five compounds, compound ZM631 showed the best antibacterial activity against methicillin-resistant S. aureus (MRSA) with the low MIC of 1 µg/mL which is 2-fold more active than that of the positive drug gepotidacin. Molecular docking study revealed that compound ZM631 fitted well in the active pockets of bacterial S. aureus DNA gyrase and formed a key hydrogen bond binding with the residue ASP-1083. These findings demonstrated that the psoralen scaffold could serve as an antibacterial lead compound for further drug development against multidrug-resistant bacterial infections.

Elucidating the biological characteristics and pathogenicity of the highly virulent G2a porcine epidemic diarrhea virus.

Since the large-scale outbreak of porcine epidemic diarrhoea (PED) in 2010, caused by the genotype 2 (G2) variant of the porcine epidemic diarrhoea virus (PEDV), pig farms in China, even those vaccinated with the G2b vaccine, have experienced infections from the G2a variant, leading to significant economic losses. This study successfully isolated the G2a strain DY2020 from positive small intestine contents (SICs) by blind passage on Vero cells for four generations. The SICs were taken from Daye, Hubei Province, China. The biological characteristics were identified by indirect immunofluorescence assay (IFA) and transmission electron microscopy (TEM). The growth kinetics of the strain on Vero cells were detected by TCID50, and the virus titre could reach 107.35 TCID50 ml-1 (SD: 5.07×106). The pathogenicity towards colostrum-deprived piglets was conducted by assessing faecal viral shedding, morphometric analysis of intestinal lesions, and immunohistochemical staining. The results showed that DY2020 was highly virulent to colostrum-deprived piglets, with severe watery diarrhoea and other clinical symptoms appeared at 6 h post-infection (h p.i.), and all died within 30 h. Pathological tissue examination results showed that the lesions mainly occurred in the intestines of piglets, causing pathological changes such as shortening of intestinal villi. In summary, the discovery of the G2a strain DY2020 in this study is of great significance for understanding Hubei PEDV and provides an important theoretical basis for the development of new efficient PEDV vaccines.

Impact of Molecular Status on Cytoreductive Surgery for Peritoneal Metastases from Colorectal Cancer.

Colorectal cancer peritoneal metastases (CRC-PM) are present in 5 to 15% of instances of CRC, and the overall survival (OS) of patients with CRC-PM is much lower than that of patients with other isolated metastatic locations. In recent years, the introduction of cytoreductive surgery (CRS) in conjunction with hyperthermic intraperitoneal chemotherapy has resulted in a significant improvement in CRC-PM patients' OS. Despite this, a significant proportion of CRS patients continue to suffer complications of grades III to V or even die during the perioperative period. Early diagnosis, optimization of patient selection criteria, and refining of individualized combination therapy are necessary for these patients. In this review, we evaluate studies examining the relationship between molecular status and CRS in CRC-PM. Our objective is to gain a comprehensive understanding of how the altered molecular status of CRC-PM impacts CRS, which could increase the likelihood of tailored therapy in the future.

A Recombinant Chimera Vaccine Composed of LTB and Mycoplasma hyopneumoniae Antigens P97R1, mhp390 and P46 Elicits Cellular Immunologic Response in Mice.

Mycoplasma hyopneumoniae is the etiological agent of porcine enzootic pneumonia (EP), leading to a mild and chronic pneumonia in swine. Relative control has been attained through active vaccination programs, but porcine enzootic pneumonia remains a significant economic challenge in the swine industry. Cellular immunity plays a key role in the prevention and control of porcine enzootic pneumonia. Therefore, the development of a more efficient vaccine that confers a strong immunity against M. hyopneumoniae is necessary. In this study, a multi-antigen chimera (L9m6) was constructed by combining the heat-labile enterotoxin B subunit (LTB) with three antigens of M. hyopneumoniae (P97R1, mhp390, and P46), and its immunogenic and antigenic properties were assessed in a murine model. In addition, we compared the effect of individual administration and multiple-fusion of these antigens. The chimeric multi-fusion vaccine induced significant cellular immune responses and high production of IgG and IgM antibodies against M. hyopneumoniae. Collectively, our data suggested that rL9m6 chimera exhibits potential as a viable vaccine candidate for the prevention and control of porcine enzootic pneumonia.

Tea Polyphenols Protects Tracheal Epithelial Tight Junctions in Lung during Actinobacillus pleuropneumoniae Infection via Suppressing TLR-4/MAPK/PKC-MLCK Signaling.

Actinobacillus pleuropneumoniae (APP) is the causative pathogen of porcine pleuropneumonia, a highly contagious respiratory disease in the pig industry. The increasingly severe antimicrobial resistance in APP urgently requires novel antibacterial alternatives for the treatment of APP infection. In this study, we investigated the effect of tea polyphenols (TP) against APP. MIC and MBC of TP showed significant inhibitory effects on bacteria growth and caused cellular damage to APP. Furthermore, TP decreased adherent activity of APP to the newborn pig tracheal epithelial cells (NPTr) and the destruction of the tight adherence junction proteins ß-catenin and occludin. Moreover, TP improved the survival rate of APP infected mice but also attenuated the release of the inflammation-related cytokines IL-6, IL-8, and TNF-α. TP inhibited activation of the TLR/MAPK/PKC-MLCK signaling for down-regulated TLR-2, TLR4, p-JNK, p-p38, p-PKC-α, and MLCK in cells triggered by APP. Collectively, our data suggest that TP represents a promising therapeutic agent in the treatment of APP infection.

Recognition of outer membrane proteins using multiple feature fusion.

Introduction: Outer membrane proteins are crucial in maintaining the structural stability and permeability of the outer membrane. Outer membrane proteins exhibit several functions such as antigenicity and strong immunogenicity, which have potential applications in clinical diagnosis and disease prevention. However, wet experiments for studying OMPs are time and capital-intensive, thereby necessitating the use of computational methods for their identification. Methods: In this study, we developed a computational model to predict outer membrane proteins. The non-redundant dataset consists of a positive set of 208 outer membrane proteins and a negative set of 876 non-outer membrane proteins. In this study, we employed the pseudo amino acid composition method to extract feature vectors and subsequently utilized the support vector machine for prediction. Results and Discussion: In the Jackknife cross-validation, the overall accuracy and the area under receiver operating characteristic curve were observed to be 93.19% and 0.966, respectively. These results demonstrate that our model can produce accurate predictions, and could serve as a valuable guide for experimental research on outer membrane proteins.

The adcA and lmb Genes Play an Important Role in Drug Resistance and Full Virulence of Streptococcus suis.

Streptococcus suis is an recognized zoonotic pathogen of swine and severely threatens human health. Zinc is the second most abundant transition metal in biological systems. Here, we investigated the contribution of zinc to the drug resistance and pathogenesis of S. suis. We knocked out the genes of AdcACB and Lmb, two Zn-binding lipoproteins. Compared to the wild-type strain, we found that the survival rate of this double-mutant strain (ΔadcAΔlmb) was reduced in Zinc-limited medium, but not in Zinc-supplemented medium. Additionally, phenotypic experiments showed that the ΔadcAΔlmb strain displayed impaired adhesion to and invasion of cells, biofilm formation, and tolerance of cell envelope-targeting antibiotics. In a murine infection model, deletion of the adcA and lmb genes in S. suis resulted in a significant decrease in strain virulence, including survival rate, tissue bacterial load, inflammatory cytokine levels, and histopathological damage. These findings show that AdcA and Lmb are important for biofilm formation, drug resistance, and virulence in S. suis. IMPORTANCE Transition metals are important micronutrients for bacterial growth. Zn is necessary for the catalytic activity and structural integrity of various metalloproteins involved in bacterial pathogenic processes. However, how these invaders adapt to host-imposed metal starvation and overcome nutritional immunity remains unknown. Thus, pathogenic bacteria must acquire Zn during infection in order to successfully survive and multiply. The host uses nutritional immunity to limit the uptake of Zn by the invading bacteria. The bacterium uses a set of high-affinity Zn uptake systems to overcome this host metal restriction. Here, we identified two Zn uptake transporters in S. suis, AdcA and Lmb, by bioinformatics analysis and found that an adcA and lmb double-mutant strain could not grow in Zn-deficient medium and was more sensitive to cell envelope-targeting antibiotics. It is worth noting that the Zn uptake system is essential for biofilm formation, drug resistance, and virulence in S. suis. The Zn uptake system is expected to be a target for the development of novel antimicrobial therapies.

Computational identification of promoters in Klebsiella aerogenes by using support vector machine.

Promoters are the basic functional cis-elements to which RNA polymerase binds to initiate the process of gene transcription. Comprehensive understanding gene expression and regulation depends on the precise identification of promoters, as they are the most important component of gene expression. This study aimed to develop a machine learning-based model to predict promoters in Klebsiella aerogenes (K. aerogenes). In the prediction model, the promoter sequences in K. aerogenes genome were encoded by pseudo k-tuple nucleotide composition (PseKNC) and position-correlation scoring function (PCSF). Numerical features were obtained and then optimized using mRMR by combining with support vector machine (SVM) and 5-fold cross-validation (CV). Subsequently, these optimized features were inputted into SVM-based classifier to discriminate promoter sequences from non-promoter sequences in K. aerogenes. Results of 10-fold CV showed that the model could yield the overall accuracy of 96.0% and the area under the ROC curve (AUC) of 0.990. We hope that this model will provide help for the study of promoter and gene regulation in K. aerogenes.

Theaflavin Ameliorates Streptococcus suis-Induced Infection In Vitro and In Vivo.

Streptococcus suis (S. suis) is one of the most important zoonotic pathogens that threaten the lives of pigs and humans. Even worse, the increasingly severe antimicrobial resistance in S. suis is becoming a global issue. Therefore, there is an urgent need to discover novel antibacterial alternatives for the treatment of S. suis infection. In this study, we investigated theaflavin (TF1), a benzoaphenone compound extracted from black tea, as a potential phytochemical compound against S. suis. TF1 at MIC showed significant inhibitory effects on S. suis growth, hemolytic activity, and biofilm formation, and caused damage to S. suis cells in vitro. TF1 had no cytotoxicity and decreased adherent activity of S. suis to the epithelial cell Nptr. Furthermore, TF1 not only improved the survival rate of S. suis-infected mice but also reduced the bacterial load and the production of IL-6 and TNF-α. A hemolysis test revealed the direct interaction between TF1 and Sly, while molecular docking showed TF1 had a good binding activity with the Glu198, Lys190, Asp111, and Ser374 of Sly. Moreover, virulence-related genes were downregulated in the TF1-treated group. Collectively, our findings suggested that TF1 can be used as a potential inhibitor for treating S. suis infection in view of its antibacterial and antihemolytic activity.

Prediction of apoptosis protein subcellular location based on amphiphilic pseudo amino acid composition.

Introduction: Apoptosis proteins play an important role in the process of cell apoptosis, which makes the rate of cell proliferation and death reach a relative balance. The function of apoptosis protein is closely related to its subcellular location, it is of great significance to study the subcellular locations of apoptosis proteins. Many efforts in bioinformatics research have been aimed at predicting their subcellular location. However, the subcellular localization of apoptotic proteins needs to be carefully studied. Methods: In this paper, based on amphiphilic pseudo amino acid composition and support vector machine algorithm, a new method was proposed for the prediction of apoptosis proteins\x{2019} subcellular location. Results and Discussion: The method achieved good performance on three data sets. The Jackknife test accuracy of the three data sets reached 90.5%, 93.9% and 84.0%, respectively. Compared with previous methods, the prediction accuracies of APACC_SVM were improved.

Investigation of cytotoxic cadmium in aquatic green algae by synchrotron radiation-based Fourier transform infrared spectroscopy: Role of dissolved organic matter.

The heavy metal Cd can cause severe toxicity on aquatic algae, but there are few studies on the cytotoxicity of heavy metal on algae based on synchrotron radiation technology. In this study, synchrotron radiation-based Fourier transform infrared spectromicroscopy (SR-FTIR) was used to characterize in vivo the toxic effects of Cd on Cosmarium sp. cells, emphasizing the influence of dissolved organic matter (DOM) on Cd toxicity. Results showed that, in the absence of DOM, obvious growth inhibition, cell volume reduction, and photosynthesis disruption could be observed with increasing Cd concentrations (0-500 µg/L). Based on the SR-FTIR imaging and functional group quantification, it was shown that the biosynthesis of biomolecules such as proteins, lipids, and carbohydrates was inhibited in algal cells. However, the addition of DOM caused significant heterogeneities in biomacromolecule biosynthesis that an increased biosynthesis of carbohydrates and structural lipids but an inhibited biosynthesis of proteins and storage lipids were observed. Furthermore, the correlation analysis and principal component analysis showed a good correlation between v(C-OH)/Amide II and biochemical parameters, indicating that changes of carbohydrates could be used as the biomarker to indicate the cytotoxicity of heavy metals to algal cells. These findings provide insight into the mechanisms of heavy metal cytotoxicity to aquatic algae and systematic cytotoxicity assessment under various aquatic conditions.

4-Phenyl-butyric Acid Inhibits Japanese Encephalitis Virus Replication via Inhibiting Endoplasmic Reticulum Stress Response.

Japanese encephalitis virus (JEV) infection causes host endoplasmic reticulum stress (ERS) reaction, and then induces cell apoptosis through the UPR pathway, invading the central nervous system and causing an inflammation storm. The endoplasmic reticulum stress inhibitor, 4-phenyl-butyric acid (4-PBA), has an inhibitory effect on the replication of flavivirus. Here, we studied the effect of 4-PBA on JEV infection both in vitro and vivo. The results showed that 4-PBA treatment could significantly decrease the titer of JEV, inhibit the expression of the JEV NS3 protein (in vitro, p < 0.01) and reduce the positive rate of the JEV E protein (in vivo, p < 0.001). Compared to the control group, 4-PBA treatment can restore the weight of JEV-infected mice, decrease the level of IL-1ß in serum and alleviate the abnormalities in brain tissue structure. Endoplasmic reticulum stress test found that the expression level of GRP78 was much lower and activation levels of PERK and IRE1 pathways were reduced in the 4-PBA treatment group. Furthermore, 4-PBA inhibited the UPR pathway activated by NS3, NS4b and NS5 RdRp. The above results indicated that 4-PBA could block JEV replication and inhibit ER stress caused by JEV. Interestingly, 4-PBA could reduce the expression of NS5 by inhibiting transcription (p < 0.001), but had no effect on the expression of NS3 and NS4b. This result may indicate that 4-PBA has antiviral activity independent of the UPR pathway. In summary, the effect of 4-PBA on JEV infection is related to the inhibition of ER stress, and it may be a promising drug for the treatment of Japanese encephalitis.

Origin, composition, and accumulation of dissolved organic matter in a hypersaline lake of the Qinghai-Tibet Plateau.

Inland saline lakes are widely distributed and commonly exist in arid and semi-arid regions. Dissolved organic matter (DOM) in saline lakes plays an important role in the global carbon cycle and is a key regulator of saline lake ecosystem functions through biotic and abiotic processes. However, the origin, composition, and cycling of DOM in saline lakes, especially hypersaline lakes, remain largely unknown. In this study, two lake brine DOM samples and three input river DOM samples from a hypersaline lake, Da Qaidam Lake (DQL) in the Qaidam Basin of the Qinghai-Tibet Plateau (QTP), were isolated and analyzed using a multi-analytical approach. The results indicated that, although terrestrial in origin, the DOM composition and features of DQL were dominated by indigenous in-lake processes owing to the very long water residence time of the lake brine. Lake DOM contained more aliphatic compounds but fewer aromatic compounds than DOM from the rivers. Lake DOM also exhibited more chemodiversity and contained highly saturated and oxidized components that were incorporated with heteroatoms. Despite the limited contributions from riverine DOM, some special features of lake DOM, such as the high content of sulfur-bearing components, may be partly related to the long-term accumulation of hotspring riverine input. Flocculation, photodegradation, microbial degradation, evapo-concentration, and primary production processes were considered synergistic factors in the persistence and features of the hypersaline lake DOM. The results of this study can further our knowledge of the transformation and long-term turnover of DOM in hypersaline lakes and how DOM chemodiversity changes across wide aquatic ecosystems.

Discovery of Novel 3,11-Bispeptide Ester Arenobufagin Derivatives with Potential in Vivo Antitumor Activity and Reduced Cardiotoxicity.

Arenobufagin, one of the bufadienolides isolated from traditional Chinese medicine Chan'su, exhibits potent antitumor activity. However, serious toxicity and small therapeutic window limits its drug development. In the present study, to our knowledge, novel 3,11-bispeptide ester arenobufagin derivatives have been firstly designed and synthesized on the base of our previous discovery of active 3-monopeptide ester derivative. The in vitro antiproliferative activity evaluation revealed that the moiety at C3 and C11 hydroxy had an important influence on cytotoxic activity and selectivity. Compound ZM350 notably inhibited tumor growth by 58.8 % at a dose 10 mg/kg in an A549 nude mice xenograft model. Therefore, compound ZM350 also presented a concentration-dependent apoptosis induction and low inhibitory effect against both hERG potassium channel and Cav1.2 calcium channel. Our study suggests that novel 3,11-bispeptide ester derivatives will be a potential benefit to further antitumor agent development of arenobufagin.

Mutations in troABCD against Copper Overload in a copA Mutant of Streptococcus suis.

Streptococcus suis is a major swine pathogen that is increasingly recognized as a porcine zoonotic pathogen that threatens the health of both pigs and humans. Metal homeostasis plays a critical role during the process of bacterial infection. In this study, RNA sequencing was used to identify potential candidate genes involved in the maintenance of intracellular copper homeostasis. CopA was identified as the primary copper exporter in S. suis. The copA deletion mutant strain was found to be more sensitive to copper and accumulated more intracellular copper than the wild-type (WT) parent strain. In addition, adding manganese increased the ability of S. suis to resist copper, and the manganese transporter, TroABCD, was involved in tolerance to copper. The copA deletion mutant strain accumulated less copper when supplemented with manganese. Furthermore, when cultured with copper, the double deletion mutant (ΔcopAΔtroA) exhibited improved growth compared to the copA deletion mutant strain. In addition, the double deletion mutant (ΔcopAΔtroA) accumulated less copper than the copA deletion mutant strain. These data were consistent with a model wherein defective TroABCD resulted in decreased cellular copper accumulation and protected the strain against copper poisoning. IMPORTANCE Metal homeostasis plays a critical role during the process of bacterial infection. We identified three important potential candidate genes involved in maintenance of intracellular copper homeostasis. CopA was demonstrated to be the main copper exporter in Streptococcus suis, and manganese increased the tolerance of S. suis to copper. The double deletion mutant (ΔcopAΔtroA) improved growth ability over the copA deletion mutant strain in the presence of high concentrations of copper and accumulated less copper. These findings are consistent with a model wherein defective TroABCD resulted in decreased cellular accumulation of copper and protected the strain against copper poisoning.

Signaling Lymphocytic Activation Molecule Family Member 1 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication.

The porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease in domestic swine. Signaling lymphocytic activation molecule family member 1 (SLAMF1) is a costimulatory factor that is involved in innate immunity, inflammation, and infection. Here, we demonstrate that overexpression of the SLAMF1 gene inhibited PRRSV replication significantly and reduced the levels of key signaling pathways, including MyD88, RIG-I, TLR2, TRIF, and inflammatory factors IL-6, IL-1ß, IL-8, TNF-ß, TNF-α, and IFN-α in vitro. However, the knockdown of the SLAMF1 gene could enhance replication of the PRRSV and the levels of key signaling pathways and inflammatory factors. Overall, our results identify a new, to our knowledge, antagonist of the PRRSV, as well as a novel antagonistic mechanism evolved by inhibiting innate immunity and inflammation, providing a new reference and direction for PRRSV disease resistance breeding.

Metabolomics and proteomics analyses revealed mechanistic insights on the antimicrobial activity of epigallocatechin gallate against Streptococcus suis.

Streptococcus suis (S. suis) is a highly virulent zoonotic pathogen and causes severe economic losses to the swine industry worldwide. Public health security is also threatened by the rapidly growing antimicrobial resistance in S. suis. Therefore, there is an urgent need to develop new and safe antibacterial alternatives against S. suis. The green tea polyphenol epigallocatechin gallate (EGCG) with a number of potential health benefits is known for its antibacterial effect; however, the mechanism of its bactericidal action remains unclear. In the present, EGCG at minimal inhibitory concentration (MIC) showed significant inhibitory effects on S. suis growth, hemolytic activity, and biofilm formation, and caused damage to S. suis cells in vitro. EGCG also reduced S. suis pathogenicity in Galleria mellonella larvae in vivo. Metabolomics and proteomics analyses were performed to investigate the underlying mechanism of antibacterial activity of EGCG at MIC. Many differentially expressed proteins involved in DNA replication, synthesis of cell wall, and cell membrane, and virulence were down-regulated after the treatment of S. suis with EGCG. EGCG not only significantly reduced the hemolytic activity of S. suis but also down-regulated the expression of suilysin (Sly). The top three shared KEGG pathways between metabolomics and proteomics analysis were ABC transporters, glycolysis/gluconeogenesis, and aminoacyl-tRNA biosynthesis. Taken together, these data suggest that EGCG could be a potential phytochemical compound for treating S. suis infection.