Virulence
·
2025
·
IF 5.4
Zijing Liang,Shuoyue Wang,Xinchi Zhu,Jiale Ma,Huochun Yao,Zongfu Wu
Streptococcus suis is a Gram-positive pathogen causing septicaemia and meningitis in pigs and humans. However, how S. suis maintains a high bacterial load in the blood and brain is poorly understood. In this study, we found that a small RNA rss03 is predominantly present in S. suis, Streptococcus parasuis, and Streptococcus ruminantium, implying a conserved biological function. rss03 with a size of 303 nt mainly exists in S. suis sequence type (ST) 1 and epidemic ST7 strains that are responsible for human infections in China. Using MS2-affinity purification coupled with RNA sequencing (MAPS), proteomics analysis, and CopraRNA prediction, 14 direct targets of rss03 from an ST7 strain were identified. These direct targets mainly involve substance transport, transcriptional regulation, rRNA modification, and stress response. A more detailed analysis reveals that rss03 interacts with the coding region of glpF mRNA, and unexpectedly rss03 protects glpF mRNA from degradation by RNase J1. The GlpF protein is an aquaporin, contributes to S. suis oxidative stress resistance by H2O2 efflux, and facilitates bacterial survival in murine macrophages RAW264.7. Finally, we showed that rss03 and GlpF are required to maintain a high bacterial load in mouse blood and brain. Our study presents the first sRNA targetome in streptococci, enriches the knowledge of sRNA regulation in streptococci, and identifies pathways contributing to S. suis pathogenesis.
研究领域:
微生物学
·
分子生物学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
·
2026
·
IF 5
Hongdou Liu,Shichao Xu,Rui Lei,Xiaoying Yu,Yi Lu,Yandi Pan,Bo Su,Shiqi Lang,Hongkai Ren,Rendong Fang,Jialu Zhang,Lianci Peng
Celastrol exhibits effective anti- S. suis efficacy both in vitro and in vivo. • Celastrol potentiates the anti- S. suis efficacy of antibiotics. • Celastrol potentially targets arginine deiminase (ADI) and disrupts arginine metabolism of S. suis . • Celastrol disrupts cytoplasmic membrane function of S. suis . Objectives : Given the rising prevalence of Streptococcus suis ( S. suis ) infection and the reduced effectiveness of traditional antibiotics, the development of novel alternative therapeutics or synergistic adjuvants to improve antimicrobial efficacy is urgently required. Celastrol displays antibacterial effects, but the specific mechanism by which celastrol exerts its anti- S. suis activity through interference with arginine metabolism remains unexplored. Purpose : This study investigated the antibacterial mechanism of celastrol against S. suis and further demonstrated its potential as an adjuvant to conventional antibiotics. Methods : The in vitro and in vivo anti- S. suis efficacy of celastrol were evaluated through time-killing curves, drug resistance, biofilm formation assays and mice infection model. The synergistic efficacy of celastrol and antibiotics against S. suis was evaluated through checkerboard microdilution assay. Transcriptomic analysis was performed to analyze the potential anti- S. suis pathways of celastrol. Anti- S. suis target of celastrol was elucidated using Δ arcA mutant strain, CETSA and DARTS assays. Celastrol-disrupted membrane integrity and function of S. suis were employed. Results : Celastrol exerted potent anti- S. suis efficacy in vitro and in vivo , and combination with antibiotics exhibited synergistic antibacterial efficacy. We found that celastrol treatment downregulated arginine-metabolism genes including arcA, argF , and argR . Importantly, celastrol physically interacted with recombinant ADI, the key enzyme catalyzing arginine degradation. Meanwhile, celastrol destroyed membrane integrity, induced ROS accumulation, caused proton motive force (PMF) dissipation, impaired ATP production and inhibited efflux pump activity. Conclusion : This study demonstrates that celastrol exerts anti- S. suis efficacy by disrupting arginine metabolism and compromising membrane function. Download: Download high-res image (259KB) Download: Download full-size image
✓ 已验证
产品关联
DOI
高影响因子
Virulence
·
2025
·
IF 5.4
Qingying Fan,Haikun Wang,Shuo Yuan,Yingying Quan,Rishun Li,Li Yi,Aiqing Jia,Yuxin Wang,Yang Wang
Streptococcus suis, a zoonotic pathogen, is commonly found as a commensal bacterium in the respiratory tracts of pigs. Under specific conditions, it becomes invasive and enters the blood, causing severe systemic infections. For S. suis, effective acquisition of carbon sources in different host niches is necessary for its survival. However, as of now, our understanding of the metabolism of S. suis within the host is highly restricted. Pyruvate formate lyase (PFL) plays a crucial role in bacterial survival of in glucose-limited and hypoxic host tissues. Here, we investigated the physiological and metabolic functions of PFL PflB in S. suis and elucidated its pivotal role in regulating virulence within the mucosal and blood niches. We demonstrate that PflB is a key enzyme for S. suis to support mixed-acid fermentation under glucose-limited and hypoxic conditions. Additionally, PflB is involved in regulating S. suis morphology and stress tolerance, and its regulation of capsular polysaccharide content depends on dynamic carbon availability. We also found that PflB is associated with the capacity of S. suis to cause bacteremia and persist in the upper respiratory tract to induce persistent infection. Our results provide highly persuasive evidence for the relationship between metabolic regulation and the virulence of S. suis.
研究领域:
微生物学
·
感染病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 18
·14211
·
IF 5.6
Jie Li,Ning Han,Yangyang Li,Feifei Zhao,Wenguang Xiong,Zhenling Zeng
Streptococcus suisis an emerging zoonotic pathogen that can cause fatal diseases such as meningitis and sepsis in pigs and human beings. The overuse of antibiotics is leading to an increased level of resistance inS. suis, and novel antimicrobial agents or anti-virulence agents for the treatment of infections caused byS. suisare urgently needed. In the present study, we investigated the antibacterial activity, mode of action and anti-virulence effects of floxuridine againstS. suis. Floxuridine showed excessive antibacterial activity againstS. suisboth in vivo and in vitro; 4 × MIC of floxuridine could killS. suiswithin 8 h in a time–kill assay. Meanwhile, floxuridine disrupted the membrane structure and permeability of the cytoplasmic membrane. Molecular docking revealed that floxuridine and SLY can be directly bind to each other. Moreover, floxuridine effectively inhibited the hemolytic capacity and expression levels of the virulence-related genes ofS. suis. Collectively, these results indicate that the FDA-approved anticancer drug floxuridine is a promising agent and a potential virulence inhibitor againstS. suis.Keywords:floxuridine;Streptococcus suis;mode of action;anti-virulence
研究领域:
微生物学
·
药理学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
·
2025
·
IF 7.7
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.
研究领域:
微生物学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 8
·7354
·
IF 5.6
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
研究领域:
微生物学
·
传染病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
·
2025
·
IF 4.6
Yi Lu,Xiaoying Yu,Yandi Pan,Hang Yin,Qingqing Yang,Xin Shen,Xuefeng Cao,Zhiwei Li,Lianci Peng,Rendong Fang
With the increased bacterial resistance to conventional antibiotics, there is an urgent need for the development of novel antimicrobial agents. Cathelicidins belonging to the family of cationic host defense peptides (HDPs) are a critical component of the innate immune system with antimicrobial and immunomodulatory activities. Our previous study has shown that CATH-1 exhibits potent bactericidal activity against Streptococcus suis ( S. suis ), but the underlying mechanism is still unclear. In this study, we investigated the effect of CATH-1 on the resistance development and antibacterial mechanisms against S. suis strain SC19. Our results revealed that CATH-1 did not induce bacterial drug-resistance. Proteomics and metabolomics analyses revealed that CATH-1 exerts its antibacterial effects by modulating multiple pathways, including the cell membrane, bacterial virulence, and energy metabolism pathway. Mechanistically, CATH-1 exerts dual antimicrobial effects by disrupting bacterial membrane integrity and targeting the serine/threonine kinase (STK) to inhibit capsular polysaccharide (CPS) synthesis. The interaction between STK and CATH-1 was evident by molecular docking, GST affinity-isolation assay, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS). Furthermore, stk deficiency abrogated the anti- S. suis efficacy of CATH-1 both in vitro bactericidal assay and in vivo infection model, indicating that STK is the potential target of CATH-1. Our study reveals a novel antibacterial target of CATH-1, providing new insights into the development of antimicrobial peptides as anti-infective agents.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
VACCINE
·
2025
·
IF 3.5
Yingjie Zhong,Huimin Yang,Wenqin Chai,Danyu Chen,Yannan Xue,Min Li,Xiongyan Meng,Shuai Meng,Jing-Ren Zhang,Chao Wu,Chengli Zong
Streptococcus suis serotype 2 (SS2) is a major zoonotic pathogen responsible for severe infections in both pigs and humans. Despite its clinical significance, no effective vaccine is currently available, and the influence of capsular polysaccharide (CPS2) structural features on host immunity remains unclear. Here, we identified a fast-growing SS2 strain from a panel of 40 clinical isolates and established a novel, reliable CPS2 purification method. This approach combines polyethylenimine-mediated nucleic acid precipitation with phenol-based protein denaturation, eliminating the need for column chromatography and enabling gram-scale CPS2 recovery per liter of culture while preserving structural integrity. To examine the role of sialic acid, we compared antibody responses induced by native and desialylated CPS2 conjugates in mice, which revealed no significant differences. Based on this finding, a native CPS2 conjugate vaccine was subsequently evaluated in pigs, where it induced robust IgG responses and conferred significant protection against virulent SS2 challenge. The effects of different adjuvants and dosages were also investigated. Collectively, these results establish an efficient CPS2 production platform, clarify the limited impact of sialic acid on conjugate-induced antibody responses, and highlight the potential of CPS2-based conjugates as promising vaccine candidates against SS2 infection.
研究领域:
微生物学
·
疫苗学
·
免疫学
·
传染病学
·
人畜共患病原体
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Qianwei Qu,Wenqiang Cui,Xingyu Huang,Zhenxin Zhu,Yue Dong,Zhongwei Yuan,Chunliu Dong,Yadan Zheng,Xueying Chen,Shuguang Yuan,Yanhua Li
Due to the large amount of antibiotics used for human therapy, agriculture, and even aquaculture, the emergence of multidrug-resistant Streptococcus suis (S. suis) led to serious public health threats. Antibiotic-assisted strategies have emerged as a promising approach to alleviate this crisis. Here, the polyphenolic compound gallic acid was found to enhance sulfonamides against multidrug-resistant S. suis. Mechanistic analysis revealed that gallic acid effectively disrupts the integrity and function of the cytoplasmic membrane by dissipating the proton motive force of bacteria. Moreover, we found that gallic acid regulates the expression of dihydrofolate reductase, which in turn inhibits tetrahydrofolate synthesis. As a result of polypharmacology, gallic acid can fully restore sulfadiazine sodium activity in the animal infection model without any drug resistances. Our findings provide an insightful view into the threats of antibiotic resistance. It could become a promising strategy to resolve this crisis.
研究领域:
微生物学
·
药理学
·
传染病
·
抗菌素耐药性
✓ 已验证
DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2026
·
IF 2.8
Haikun Wang,Qingying Fan,Baobao Liu,Yuxin Wang,Aiqing Jia,Li Yi,Yang Wang
In bacteria, the glycosyltransferases play important roles in bacterial fitness and virulence. A prior transposon screen implicated glycosyltransferase Gtf-2 in the regulation of S. suis biofilm formation, but the biological function of Gtf-2 and how biofilm is modulated by Gtf-2 remains largely unclear. Here, we characterized the major components of S. suis biofilm matrix and further elucidated the its regulatory role in biofilm formation, which involved the regulation of S. suis extracellular matrix, c-di-AMP, cell surface properties, and bacterial energy metabolism. Additionally, we also revealed that Gtf-2 regulates the content and composition of capsular polysaccharide. Finally, the regulatory role of Gtf-2 in the virulence of S. suis was elucidated based on in vitro and in vivo infection models, and the loss of Gtf-2 function weakened the virulence of S. suis .
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Virulence
·
2025
·
IF 5.4
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.
研究领域:
微生物学
·
感染病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）