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ENVIRONMENTAL RESEARCH · 2025 · IF 7.7

Effects of Environment Regulating T4SS on Virulence and Adaptability of Streptococcus suis

Yamin Shen,Yue Li,Yingying Quan,Wenjie Jin,Yuxin Wang,Baobao Liu,Yang Wang

s Streptococcus suis ( S. suis ) represents a significant bacterial pathogen, with its zoonotic transmission from infected or deceased pigs to humans posing a serious threat to public health. The type IV secretion system (T4SS), a critical virulence factor of S. suis , is tightly regulated by diverse environmental conditions. This study explores the influence of environmental variables, including temperature, incubation duration, monosaccharides, and metal ions, on the regulation of T4SS in S. suis and its associated pathogenicity. Results revealed that T4SS expression peaked during the stabilization phase at 37 °C, with galactose markedly enhancing T4SS expression relative to glucose. Zinc ions specifically enhanced the expression of the T4SS effector SspA among various metal ions. Moreover, zinc exposure significantly augmented both T4SS and virulence gene expression capabilities in S. suis . Zinc-treated S. suis exhibited enhanced adhesion, invasion, and colonization capacity in Hep-2 cells, Raw264.7 cells, and mouse models. These findings provide a deeper comprehension of the environmental modulation of T4SS in S. suis , paving the way for advanced studies into its mechanisms of pathogenicity.

CAS / MDL: 50-99-7 15572-79-9
研究领域: 微生物学 · 感染病学
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PHYTOMEDICINE · 2025 · IF 8.3

Effect of emodin on Streptococcus suis by targeting β-ketoacyl-acyl carrier protein synthase Ⅱ

Jun Wang,Yongzheng Liu,Chongxiang Sun,Long Chen,Sikai Chen,Xingyu Huang,Zhijia Lu,Chunliu Dong,Yadan Zheng,Zhiyun Zhang,Yanyan Liu,Qianwei Qu,Yanhua Li

Background : Streptococcus suis is a zoonotic pathogen that causes meningitis, septicaemia, endocarditis, arthritis, and pneumonia in human beings. With the increasing prevalence of S. suis infections and a general decline in the effectiveness of antibiotics, the development of novel drugs that have effect on S. suis is extremely urgent. Emodin, a natural anthraquinone derivative of Rheum palmatum L., Reynoutria japonica Houtt., Polygonum multiflorum Thunb. and Cassia obtusifolia L., has been reported to exert anti- S. suis effect; however, the specific mechanism of the anti- S. suis action by targeting β-ketoacyl-acyl carrier protein synthase Ⅱ (FabF) in the fatty acid synthesis pathway remains unexplored. Purpose: We sought to reveal the potential role of emodin to prevent S. suis infection, investigate its mechanism of anti- S. suis action, and provide further evidence of emodin as an alternative to traditional antibiotic agents. Methods : The in vitro anti- S. suis properties of emodin were assessed through minimum inhibitory concentration (MIC) assays, and time-kill assays. Subsequently, the mechanisms underlying emodin’s mode of action at the molecular level by targeting FabF were elucidated using molecular docking, site-directed mutagenesis, bio-layer interferometry assays, and cellular thermal shift assays. Finally, metabolomics, cell membrane phospholipid content assay and biochemical parameters assays were used to detect emodin disrupting cell membrane integrity and function by affecting fatty acid biosynthesis. Results : In this study, we have identified that emodin inhibits S. suis by suppressing free fatty acids (FFAs) synthesis and disrupting phospholipid production by targeting FabF, a key enzyme in the fatty acid biosynthesis pathway. This interference compromises the integrity and functionality of the cell membranes of S. suis . Emodin also triggers the dissipation of the proton motive force, accelerates the tricarboxylic acid cycle, and enhances cellular respiration, ultimately leading to S. suis cell death. Conclusion : This study suggested that emodin inhibits the growth of S. suis via targeting FabF and the inhibition of fatty acid biosynthesis through enzyme-targeted drug design. This represents a novel strategy for developing antimicrobial agents against S. suis and addressing the challenge of antibiotic resistance.

研究领域: 微生物学 · 药理学
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Computational Intelligence and Neuroscience · 2022 · IF 3.12

Omadacycline Efficacy against Streptococcus Agalactiae Isolated in China: Correlation between Resistance and Virulence Gene and Biofilm Formation

Guiqiu Li,Ying Wei,Yan Guo,Hui Gong,Jie Lian,Guangjian Xu,Bing Bai,Zhijian Yu,Qiwen Deng

This study aimed to evaluate the activity, resistance, clonality of MIC distribution, and the correlation between virulence and resistance genes and biofilm formation of omadacycline (OMC) in clinics for Streptococcus agalactiae isolates from China. 162 isolates were collected retrospectively in China. The S. agalactiae were collected from the body’s cervical secretions, wound secretions, ear swabs, secretions, semen, venous blood, cerebrospinal fluid, pee, etc. The MIC of OMC against S. agalactiae was determined by broth microdilution. The inhibition zone diameters of OMC and other common antibiotics were measured using filter paper. D-test was performed to determine the phenotype of cross resistance between erythromycin and clindamycin. In Multilocus sequence typing (MLST), some commonly-detected resistance genes and virulence gene of these S. agalactiae isolates were investigated using polymerase chain reaction (PCR). Biofilms were detected by crystal violet staining. Our data demonstrated the correalation of the biofilm formation and OMA antimicrobial susceptibility of S.agalactiae clinical isolates with the carrier of virulence gene scpB. Conclusively, OMC exhibits the robust antimcirobial activity against clinical S. agalactiae isolates from China compared with DOX or MIN, and the carrier of the virulence gene scpB might correlate with the biofilm formation in OMC-resistant S. agalactiae.

研究领域: 微生物学 · 感染病学 · 临床医学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

A novel α-amylase from Streptococcus thermophilus 17140 with β-glycosidic bond hydrolysis capability for the transformation of rare ginsenosides

Jinxia Liu,Xinyi Liu,Zhaoqing Song,Wenying Cao,Yue Li,Mingyu Xia,Dong Wang

Alpha-amylases typically act on starch and oligosaccharides that contain α-1,4 glycosidic linkages, while ginsenosides primarily consist of β-1,2 and β-1,6 glycosidic bonds, which cannot be hydrolyzed by α-amylases. However, for the first time, we have successfully isolated Streptococcus thermophilus 17140 (St17140), capable of converting ginsenoside Rb1 into rare ginsenosides. St17140 expresses a novel α-amylase (StAMY), which hydrolyzes ginsenoside Rb1 to produce Rd, gypenoside XVII, F 2 , and Rh 2 . With Rb 1 as the substrate, the optimal reaction temperature is 50 °C and the optimal pH is 5.5. When Rb 1 , Rd, or gypenoside XVII are used as substrates, the Km are 0.135 mM, 0.0871 mM, and 0.260 mM respectively, the Kcat are 0.621 min −1 , 0.397 min −1 , and 0.297 min −1 respectively, and the Kcat/Km are 4.59 min −1 ·mM −1 , 4.56 min −1 ·mM −1 and 1.14 min −1 ·mM −1 respectively. Utilizing molecular docking and site-directed mutagenesis techniques, the mechanism of ginsenoside hydrolysis by StAMY was further elucidated. A107, F201, A337 and A268 are key amino acid residues that anchor the saponin in the active pocket, and D234 and D331 as catalytic amino acid residues to hydrolyze ginsenosides into rare ginsenosides. It is the first time to discover a novel α-amylase with the ability to hydrolyze ginsenosides β-1,2 and β-1,6 glycosidic linkage, and the first time to discover the ability of S. thermophilus to transform rare ginsenosides. These not only enrich the resources of glycosidases and offer novel insights for the rational modification of glycosidase, also are important for further elucidating the mechanism of probiotic transformation of rare ginsenosides and developing engineering bacteria with high production of rare ginsenosides.

研究领域: 生物化学 · 微生物学 · 药理学
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ARCHIVES OF ORAL BIOLOGY · 2015 · IF 1.735

Antimicrobial effects of a bioactive glass combined with fluoride or triclosan on Streptococcus mutans biofilm

Yu-Ting Xu,Qiong Wu,Ya-Ming Chen,Roger J. Smales,Shu-Ya Shi,Meng-Ting Wang

Objective The objective of this study was to investigate the antibacterial effects on a cariogenic biofilm of a bioactive glass (BAG) combined with either sodium fluoride (NaF) or triclosan (TCS). Design According to minimal bactericidal concentrations, 37.5   mg/ml of BAG, 4.69   mg/ml of NaF, and 15.53   μg/ml of TCS solutions were prepared. When used alone, the three antimicrobial solutions were increased to double-dosage strength (2MBC). The study contained the following experimental groups: group 1, BAG (2MBC); group 2, NaF (2MBC); group 3, TCS (2MBC); group 4, BAG   +   NaF; group 5, BAG   +   TCS; group 6, control (saline). Streptococcus mutans biofilm was cultured with 0.1% sucrose anaerobically on 66 sterilized coverslips (1   ×   1   cm 2 ) for 24   h uninterrupted. After 10   min of exposure to the experimental groups, the microbial kinetics, morphology, and viability of the S. mutans biofilms were assessed by evaluation of colony-forming units (CFUs), scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM). Results BAG (2MBC) used alone showed significantly stronger antibacterial effects than the other two antimicrobials used alone. The combination groups also displayed the same or greater biofilm inactivation effects as BAG (2MBC) in the plate count test. SEM showed smaller stacks (towers) and fewer surrounding bacteria in groups BAG (2MBC), BAG   +   NaF, and BAG   +   TCS. Confocal microscopy also determined higher live/dead ratios in groups NaF (2MBC), TCS (2MBC), and control than in groups BAG (2MBC), BAG   +   NaF, and BAG   +   TCS. Conclusions The combinations of BAG with either NaF or TCS enhanced the inactivation effects of BAG (2MBC) on S. mutans biofilm, and these findings should be further investigated clinically for the control of dental biofilms.

研究领域: 口腔医学 · 微生物学 · 材料科学
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Scientific Reports · 2016 ·Vol. 6 ·期 1 ·1-10 · IF 5.228

Engineering a Carbohydrate-processing Transglycosidase into Glycosyltransferase for Natural Product Glycodiversification

Liang Chaoning,Zhang Yi,Jia Yan,Wenzhao Wang,Li Youhai,Lu Shikun,Jin Jian-Ming,Tang Shuang-Yan

Glycodiversification broadens the scope of natural product-derived drug discovery. The acceptor substrate promiscuity of glucosyltransferase-D (GTF-D), a carbohydrate-processing enzyme from Streptococcus mutans , was expanded by protein engineering. Mutants in a site-saturation mutagenesis library were screened on the fluorescent substrate 4-methylumbelliferone to identify derivatives with improved transglycosylation efficiency. In comparison to the wild-type GTF-D enzyme, mutant M4 exhibited increased transglycosylation capabilities on flavonoid substrates including catechin, genistein, daidzein and silybin, using the glucosyl donor sucrose. This study demonstrated the feasibility of developing natural product glycosyltransferases by engineering transglycosidases that use donor substrates cheaper than NDP-sugars, and gave rise to a series of α-glucosylated natural products that are novel to the natural product reservoir. The solubility of the α-glucoside of genistein and the anti-oxidant capability of the α-glucoside of catechin were also studied.

研究领域: 生物化学 · 药物开发 · 合成生物学
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Nature Biomedical Engineering · 2025 · IF 26.6

Enantiomer-dependent and modification-free DNA matrix as an adjuvant for subunit vaccines against SARS-CoV-2 or pneumococcal infections

Li Cuifeng,Li Yuxin,Zhou Bini,Li Tong,Wei Xiaohui,Chen Kun,Chen Wenlong,Shi Ziwei,Dai Xiaobin,Zhang Jiachen,Yang Chen,Ji Zhenglin,Sun Wenbo,Gao Ji,Wu Jing,Zhao Binbin,Min Xin,Li Yujie,Lin Lin,Yang Wei,Wang Min,Liu Zezhong,Liu Yaping,Zhu Chenyou,Yang Bo,Xu Jiang-Fei,Yan Li-Tang,Shi Yi,Lu Lu,Zhang Linqi,Ding Qiang,Xue Jing,Hou Baidong,Qi Hai,Liu Jiangning,Yang Yuhe R.,Liu Dongsheng,Liu Wanli

The emergence of novel infectious disease has intensified demand for more advanced vaccine development and more potent adjuvants to enhance immunogenicity. Here we introduce a dynamic DNA supramolecular matrix assembled from five unmodified, short DNA single strands, serving as a safe, multifaceted adjuvant platform. This DNA matrix elicits a robust humoral response with minimal adverse effects, generating potent neutralizing antibodies and conferring robust protection against SARS-CoV-2 and Streptococcus pneumoniae infections. Its dynamic colloidal feature prolongs the in vivo retention of both DNA and antigen, facilitating lymphatic-targeted transportation and presentation. This process leads to a robust pro-inflammatory response in both the vaccinated site and draining lymph node, which, in turn, promotes the recruitment and activation of immune cells, leading to a rapid, effective antigen-specific antibody response. The enhanced function of DNA matrix depends on the canonical TLR9–MyD88 signalling axis in dendritic cells. In addition, only right-handed, not left-handed, chirality of the DNA strands forms d -DNA matrix and promotes immune activations. Thus, this DNA matrix functions as an all-in-one adjuvant platform, opening promising avenues for future vaccine design.

研究领域: 免疫学 · 微生物学 · 生物材料 · 疫苗学
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Virulence · 2025 · IF 5.4

Guanosine enhances the bactericidal effect of ceftiofur sodium on Streptococcus suis by activating bacterial metabolism

Yue Dong,Xiaona Liu,Shanshan Xiong,Mingyu Cao,Haojie Wu,Long Chen,Mengmeng Zhao,Yadan Zheng,Zhiyun Zhang,Yanyan Liu,Yanhua Li,Qianwei Qu,Chunliu Dong

The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. Streptococcus suis (S. suis) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant S. suis. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) in vitro and in vivo. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of S. suis infection.

CAS / MDL: 53213-94-8
研究领域: 微生物学 · 感染病学 · 药理学
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CARIES RESEARCH · 2018 ·Vol. 53 ·期 2 ·176-193 · IF 2.188

A Membrane-Targeted Peptide Inhibiting PtxA of Phosphotransferase System Blocks Streptococcus mutans

Xiang Shao-Wen,Shao Jun,He Jian,Wu Xin-Yu,Xu Xiao-Hu,Zhao Wang-Hong

Streptococcus mutans, the primary cause of dental caries, takes up carbohydrates through the phosphoenolpyruvate sugar phosphotransferase system (PTS). This study aimed to identify a novel membrane-targeted antimicrobial peptide (AMP) that could also target the L-ascorbate-specific PtxA component of the S. mutans PTS system. C10-KKWW was identified and selected using virtual screening of a lipopeptide library, a minimum inhibiting concentration (MIC) assay, cytotoxicity assays and a hemolysis assay. Surface plasmon resonance confirmed that C10-KKWW had a high binding affinity for PtxA. Combining with scanning electron microscopy and cell permeability assay, it was shown that the effects of C10-KKWW could be attributed to both membrane and PtxA. Wild type (WT) S. mutans, a ptxA deletion mutant (ΔptxA), and a mutant-complemented strain (CptxA), were cultured consistently in brain heart infusion (BHI) medium, tryptone-vitamin medium supplemented with 15 mM L-ascorbate (TVL), or for 5 h in BHI supplemented with 7.4 mM sodium L-ascorbate. Compared to ∆ptxA, in WT S. mutans and CptxA, C10-KKWW had a stronger MIC (3.9 μg/mL), and distinctively decreased biofilm viability. The extracellular concentrations of L-ascorbate/sodium L-ascorbate were not changed before and after WT treated with C10-KKWW. L-ascorbate-induced operon genes, or other PTS genes, were significantly suppressed by C10-KKWW. In conclusion, C10-KKWW has been developed; it acts through interaction with the bacterial membrane and interferes with L-ascorbate translocation to inhibit S. mutans growth and eradicate its biofilm. C10-KKWW may be especially effective at optimal oral ascorbate levels. A combination of C10-KKWW with sodium L-ascorbate might also be a novel strategy for dental caries treatment

研究领域: 微生物学 · 口腔医学 · 分子生物学
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Nutrients · 2022 ·Vol. 14 ·期 5 ·1013 · IF 6.706

Gut Microbiota Composition in Relation to the Metabolism of Oral Administrated Resveratrol

Mingfei Yao,Yiqiu Fei,Shuobo Zhang,Bo Qiu,Lian Zhu,Fang Li,Björn Berglund,Hang Xiao,Lanjuan Li

Resveratrol (RSV) has been confirmed to confer multiple health benefits, and the majority of RSV tends to be metabolized in the gut microbiota after oral administration. In this study, the metabolism of RSV was investigated by using mouse models with distinct gut microbiota compositions: germ-free mice colonized with probiotics, conventional mouse, and DSS-induced colitis mouse models. The results demonstrated that in feces, the metabolites of RSV, including resveratrol sulfate (RES-sulfate), resveratrol glucuronide (RES-glucuronide), and dihydroresveratrol, significantly increased after probiotics colonized in germ-free mice. Furthermore, RES-sulfate and RES-glucuronide were below the detectable limit in the feces of conventional mice, with dihydroresveratrol being the dominant metabolite. Compared to the conventional mice, the ratio ofFirmicutes/Bacteroidesand the abundance ofLactobacillusgenera were found significantly elevated in colitis mice after long-term ingestion of RSV, which shifted the metabolism of RSV in return. Our study provided critical implications in further application of RSV in foods and food supplements.Keywords:resveratrol (RSV);metabolites;gut microbiota;mouse model;Ligilactobacillus salivariousLi01

研究领域: 营养学 · 微生物学 · 药理学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 8 ·7354 · IF 5.6

Isopropoxy Benzene Guanidine Ameliorates Streptococcus suis Infection In Vivo and In Vitro

Ning Han,Jie Li,Feifei Zhao,Yangyang Li,Jun Wang,Xiaolan Dai,Dongping Zeng,Wenguang Xiong,Zhenling Zeng

Streptococcus suis, an encapsulated zoonotic pathogen, has been reported to cause a variety of infectious diseases, such as meningitis and streptococcal-toxic-shock-like syndrome. Increasing antimicrobial resistance has triggered the need for new treatments. In the present study, we found that isopropoxy benzene guanidine (IBG) significantly attenuated the effects caused byS. suisinfection, in vivo and in vitro, by killingS. suisand reducingS. suispathogenicity. Further studies showed that IBG disrupted the integrity ofS. suiscell membranes and increased the permeability ofS. suiscell membranes, leading to an imbalance in proton motive force and the accumulation of intracellular ATP. Meanwhile, IBG antagonized the hemolysis activity of suilysin and decreased the expression ofSlygene. In vivo, IBG improved the viability ofS. suisSS3-infected mice by reducing tissue bacterial load. In conclusion, IBG is a promising compound for the treatment ofS. suisinfections, given its antibacterial and anti-hemolysis activity.Keywords:Streptococcus suis;isopropoxy benzene guanidine;antibacterial;anti-hemolysis;suilysin

CAS / MDL: 25535-16-4
研究领域: 微生物学 · 传染病学 · 药理学
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TALANTA · 2017 · IF 4.162

Specific chemiluminescent protocol for dual-site recognition of Streptococcus mutans utilizing strong affinity between teicoplanin and Gram-positive bacteria

Xiaoxiao Su,Mengyao Wang,Yue Wu,Yong He,Zhifeng Fu

A novel dual-site recognition protocol was developed for chemiluminescent (CL) detection of Streptococcus mutans ( S. mutans ) based on a designed antibiotic-affinity strategy. Teicoplanin , a broad-spectrum antibiotic against Gram-positive bacteria, was adopted to functionalize magnetic particles and recognize S. mutans utilizing the strong affinity between this agent and D-Alanyl-D-Alanine peptide moieties in the bacterial cell wall. To achieve ideal specificity for S. mutans detection, rat immunoglobulin G2a (rat IgG2a) tagged with horseradish peroxidase (HRP) was used as the second recognition agent and signal tracer since Fab region of rat IgG2a could bind with streptococcal protein G highly expressed in the cell wall of S. mutans . Thus HRP-tagged sandwich complex of teicoplanin/ S. mutans /rat IgG2a was formed on the magnetic particles, followed by a CL quantification of S. mutans based on a HRP-catalyzed luminol-H 2 O 2 -p -iodophenol CL reaction. This dual-site recognition protocol showed a linear range of 1.0 × 10 2 –1.0 × 10 6 CFU mL −1 and a detection limit of 33 CFU mL −1 for S. mutans detection. The whole detection process could be completed within 70   min. The recovery tests for food, environmental, pharmaceutical and biological samples showed acceptable recovery values between 83.0% and 110.0%, demonstrating its application potential for detection of bacteria in various sample matrixes.

研究领域: 微生物学 · 分析化学
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