MICROBIAL PATHOGENESIS
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2023
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IF 3.8
Jing Zuo,Yamin Shen,Haikun Wang,Shuji Gao,Shuo Yuan,Dong Song,Yuxin Wang,Yang Wang
Streptococcus suis ( S. suis ) regulates biofilm formation through LuxS/AI-2 quorum sensing system, increasing drug resistance and exacerbating infection. The anti-hyperglycaemic agent metformin has anti-bacterial and anti-biofilm activities. This study aimed to investigate the anti-biofilm and anti-quorum sensing activity of metformin in S. suis . We first determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of metformin on S. suis . The results indicated that metformin showed no obvious inhibitory or bactericidal effect . Crystal violet staining showed that metformin significantly inhibited the formation of S. suis biofilm at sub-MIC concentration, which was also confirmed by scanning electron microscopy. Then, we quantified the AI-2 signal molecules in S. suis , and the results showed that metformin had a significant inhibitory effect on the production of AI-2 signal in S. suis . Inhibition of enzyme activity and molecular docking experiments showed that metformin has a significant binding activity to LuxS protein. In addition, qRT-PCR results showed that metformin significantly down-regulated the expression of AI-2 synthesis-related genes luxS and pfs , and adhesion-related genes luxS , pfs , gapdh , sly , fbps, and ef . Western blotting also showed that metformin significantly reduced the expression of LuxS protein. Our study suggests that metformin seems to be a suitable candidate for the inhibition of S. suis LuxS/AI-2 QS system and prevention of biofilm formation, which provided a new idea for the prevention and control of S. suis .
研究领域:
微生物学
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药理学
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传染病学
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DOI
PubMed
高影响因子
BMC BIOLOGY
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2024
·Vol. 22
·期 1
·1-19
·
IF 4.4
Jiang Hexiang,Sun Yi,Li Fengyang,Yu Xibing,Lei Siyu,Du Sulan,Wu Tong,Jiang Xuan,Zhu Junhui,Wang Jun,Ji Yalu,Li Na,Feng Xin,Gu Jingmin,Han Wenyu,Zeng Lei,Lei Liancheng
Background Ribosomal protein SA (RPSA) of human brain microvascular endothelial cells (HBMECs) can transfer from the cytosol to the cell surface and act as a receptor for some pathogens, including Streptococcus suis serotype 2 (SS2), a zoonotic pathogen causing meningitis in pigs and humans. We previously reported that SS2 virulence factor enolase (ENO) binds to RPSA on the cell surface of HBMECs and induces apoptosis. However, the mechanism that activates RPSA translocation to the cell surface and induces ENO-mediated HBMEC apoptosis is unclear.Results Here, we show that RPSA localization and condensation on the host cell surface depend on its internally disordered region (IDR). ENO binds to the IDR of RPSA and promotes its interaction with RPSA and vimentin (VIM), which is significantly suppressed after 1,6-Hexanediol (1,6-Hex, a widely used tool to disrupt phase separation) treatment, indicating that ENO incorporation and thus the concentration of RPSA/VIM complexes via co-condensation. Furthermore, increasing intracellular calcium ions (Ca2+) in response to SS2 infection further facilitates the liquid-like condensation of RPSA and aggravates ENO-induced HBMEC cell apoptosis.Conclusion sTogether, our study provides a previously underappreciated molecular mechanism illuminating that ENO-induced RPSA condensation activates the migration of RPSA to the bacterial cell surface and stimulates SS2-infected HBMEC death and, potentially, disease progression. This study offers a fresh avenue for investigation into the mechanism by which other harmful bacteria infect hosts via cell surfaces’ RPSA.
研究领域:
微生物学
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细胞生物学
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病理学
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分子生物学
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PubMed
高影响因子
FEMS MICROBIOLOGY LETTERS
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2015
·Vol. 362
·期 6
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IF 2.121
Zhao Jianqing,Pan Shan,Lin Lan,Fu Lei,Yang Chao,Xu Zhongmin,Wei YanMin,Jin Meilin,Zhang Anding
Streptococcus suis (S. suis) ranks among the five most important porcine pathogens worldwide and occasionally threatens human health, especially in people that come into close contact with pigs or pork products. Streptococcus suis serotype 2 (SS2) is considered to be the most pathogenic and prevalent capsular type. As a first line of immune defense against SS2 infection, neutrophils can eliminate the invader not only by phagocytosis but also by neutrophil extracellular traps (NETs)-mediated killing. SS2 can resist phagocytosis through polysaccharide capsule (CPS), but how this strain evades the effects of NETs remains to be determined. The present study demonstrated that the epidemic strain 05ZY, the highly pathogenic strain P1/7 and the intermediately pathogenic strain A7 could induce the formation of NETs. Furthermore, SS2 strains could successfully resist NETs-mediated killing, and the CPS structure contributed to this resistance by escaping the trapping. Therefore, the CPS structure not only contributed to the SS2 strains’ resistance to phagocytosis-mediated killing but also played an essential role in evading NETs trapping and further killing in vitro. This study strengthens our understanding of how S. suis can evade innate immune surveillance and elimination.
研究领域:
微生物学
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免疫学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
·
IF 4.7
Yandi Pan,Hongdou Liu,Yuqian Liu,Tingting Zhang,Shichao Xu,Yilin Lu,Yi Lu,Liuyi Xu,Xiaoxiang Hu,Xuefeng Cao,Rendong Fang,Lianci Peng
With the increasing emergence of antimicrobial resistance, the rise of multidrug-resistant Streptococcus suis ( S. suis ) has caused a great threat on global public health. The combination of antimicrobial peptide (AMP) and antibiotics is an efficient strategy to enhance antibacterial efficacy and combat bacterial antibiotic resistance. In this study, the antibacterial efficacy of chicken-derived AMP CATH-1 combined with tetracycline against S. suis infection was investigated in vitro and in vivo . The results showed that combination of CATH-1 and tetracycline exerted effectively anti- S. suis activity, which rapidly killed all tested bacteria in 60 min. In the mice infection model, CATH-1 combined with tetracycline improved survival rate of SC19-infected mice, reduced bacterial load in different tissues and alleviated the inflammatory response as well as inflammatory damage. Furthermore, CATH-1 reduced the emergence of bacterial resistance to tetracycline. Mechanically, CATH-1 disrupted cell membrane via SEM observation and SYTO9/PI staining. CATH-1 in combination with tetracycline aggravated reactive oxygen species (ROS) accumulation and proton motive force (PMF) disruption compared to CATH-1 or tetracycline alone. In addition, CATH-1 inhibited efflux pump function. Importantly, we identified a critical gene steAB associated with biofilm formation and CATH-1 alone or in combination with tetracycline inhibited biofilm formation. Our study shows effective anti- S. suis infection of CATH-1-tetracycline synergy, which provides the basis on the development of AMP as additives to antibiotics.
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高影响因子
VETERINARY MICROBIOLOGY
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2021
·
IF 3.293
Hexiang Jiang,Tong Wu,Jianan Liu,Xibing Yu,Hongtao Liu,Chuntong Bao,Mengmeng Liu,Yalu Ji,Xin Feng,Jingmin Gu,Wenyu Han,Na Li,Liancheng Lei
Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes meningitis. The ubiquitously expressed 40S ribosome protein SA (RPSA) is a multifunctional protein involved in the pathogenesis of multiple pathogens, especially those causing meningitis. However, the role of RPSA in SS2-induced meningitis is not clear. In this study, immunofluorescence staining revealed that SS2 infection promoted the intracellular transfer of RPSA to the surface of human cerebral microvascular endothelial cells (HCMECs). Moreover, SS2 infection promoted the accumulation of caveolin 1 (CAV1) and the formation of membrane bulges where RPSA enveloped CAV1 on the cell surface. SS2 infection also caused dynamic changes in the localization of RPSA and CAV1 on the cell surface which could be eliminated by disruption of caveolae/rafts by addition of methyl-β-cyclodextrin (MβCD). Co-immunoprecipitation analysis demonstrated that α-enolase (ENO), a key virulence factor of SS2, interacted with RPSA, and promoted the interaction between RPSA and CAV1. Immunofluorescence staining, western blotting and flow cytometry analyses showed that damaged caveolae/rafts significantly enhanced ENO adhesion to HCMECs, promoted the “destruction” of RPSA by ENO, and enhanced the toxic effect of ENO on HCMECs. Importantly, these effects could be relieved upon the addition of cholesterol. We conclude that caveolae/rafts weaken the toxic effect of SS2 ENO on RPSA-mediated events in HCMECs. Our study has led to better understanding of the roles of RPSA and caveolae/rafts upon SS2 infection, and a new pathological role for RPSA in infection.
研究领域:
微生物学
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细胞生物学
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传染病学
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神经科学
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PubMed
高影响因子
MICROBIAL PATHOGENESIS
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2022
·
IF 3.848
Bei-Bei Dou,Xia Yang,Feng-Ming Yang,Kang Yan,Wei Peng,Jia Tang,Ming-Zheng Peng,Qi-Yun He,Huan-Chun Chen,Fang-Yan Yuan,Wei-Cheng Bei
Streptococcus suis ( S. suis ) is an important zoonotic pathogen that can cause high morbidity and mortality in both humans and swine. As the most important life-threatening infection of the central nervous system (CNS), meningitis is an important syndrome of S. suis infection. The vancomycin resistance associated sensor/regulator (VraSR) is a critical two-component signal transduction system that affects the ability of S. suis to resist the host innate immune system and promotes its ability to adhere to brain microvascular endothelial cells (BMECs). Prior work also found mice infected with Δ vraSR had no obvious neurological symptoms , unlike mice infected with wild-type SC19. Whether and how VraSR participates in the development of S. suis meningitis remains unknown. Here, we found Δ vraSR -infected mice did not show obvious meningitis, compared with wild-type SC19-infected mice. Moreover, the proinflammatory cytokines and chemokines in serum and brains of Δ vraSR- infected mice, including IL-6, TNF-α, MCP-1 and IFN-γ, were significantly lower than wild-type infected group. Besides, blood-brain barrier (BBB) permeability also confirmed that the mutant had lower ability to disrupt BBB. Furthermore, in vivo and in vitro experiments showed that SC19 could increase BBB permeability by downregulating tight junction (TJ) proteins such as ZO-1, β-Catenin, Occludin , and Clauidn-5, compared with mutant Δ vraSR . These findings provide new insight into the influence of S. suis VraSR on BBB disruption during the pathogenic process of streptococcal meningitis, thereby offering potential targets for future preventative and therapeutic strategies against this disease.
研究领域:
微生物学
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传染病学
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神经科学
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病理学
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产品关联
DOI
PubMed
高影响因子
Journal of Integrative Agriculture
·
2023
·
IF 4.8
Ke-da SHI,Yan LI,Min-sheng XU,Kun-li ZHANG,Hong-chao GOU,Shao-lun ZHAI,Chun-ling LI
Streptococcus suis serotype 2 ( S. suis 2) is a zoonotic pathogen that clinically causes severe swine and human infections (such as meningitis, endocarditis, and septicemia). In order to cause widespread diseases in different organs, S. suis 2 must colonize the host, break the blood barrier, and cause exaggerated inflammation. In the last few years, most studies have focused on a single virulence factor and its influences on the host. Membrane vesicles (MVs) can be actively secreted into the extracellular environment contributing to bacteria-host interactions. Gram-negative bacteria-derived outer membrane vesicles (OMVs) were recently shown to activate host caspase-11-mediated non-canonical inflammasome pathway via deliverance of OMV-bound lipopolysaccharide (LPS), causing host cell pyroptosis. However, little is known about the effect of the MVs from S. suis 2 (Gram-positive bacteria without LPS) on cell pyroptosis. Thus, we investigated the molecular mechanism by which S. suis 2 MVs participate in endothelial cell pyroptosis. In this study, we used proteomics, electron scanning microscopy, fluorescence microscope, western blotting, and bioassays, to investigate the MVs secreted by S. suis 2. First, we demonstrated that S. suis 2 secreted MVs with an average diameter of 72.04 nm, and 200 proteins in MVs were identified. Then, we showed that MVs were transported to cells via and dynamin-dependent endocytosis. The S. suis 2 MVs activated NLRP3/Caspase-1/GSDMD canonical inflammasome signaling pathway, resulting in cell pyroptosis, but it did not activate the caspase-4/-5 pathway. More importantly, endothelial cells produce large amounts of reactive oxygen species (ROS) and lost their mitochondrial membrane potential under induction by S. suis 2 MVs. The results in this study suggest for the first time that MVs from S. suis 2 were internalized by endothelial cells via mainly dynamin-dependent endocytosis and might promote NLRP3/caspase-1/GSDMD pathway by mitochondrial damage, which under induction produced mtDNA and ROS, leading to the pyroptosis of endothelial cells.
研究领域:
微生物学
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传染病学
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细胞生物学
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免疫学
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DOI
高影响因子
Journal of Integrative Agriculture
·
2024
·
IF 4.6
Jing Zuo,Yingying Quan,Yue Li,Dong Song,Jinpeng Li,Yuxin Wang,Li Yi,Yang Wang
Streptococcus suis is a significant zoonotic agent affecting both human and pig health and poses a substantial public health concern. The pathogenicity of S. suis is intricately linked to its ability to form biofilms and express virulence factors, which are regulated by the LuxS/AI-2 quorum sensing (QS) system. Herein, we uncover a novel therapeutic avenue by demonstrating that 5-fluorouracil (5-FU), an FDA-approved anti-cancer agent, effectively mitigates biofilm formation and attenuates the virulence of S. suis . Mechanistically, we observe a significant reduction in capsular polysaccharide and extracellular polysaccharide production upon 5-FU treatment, elucidating a potential mechanism for biofilm weakening. Additionally, 5-FU down-regulates virulence traits, diminishing S. suis ‘s ability to adhere to host cells and evade phagocytosis. Crucially, our study identifies the thymidylate synthase regulatory gene thyA as a key mediator of 5-FU’s effects on the LuxS/AI-2 QS system. Virtual molecular docking and gene knockout experiments provide compelling evidence that 5-FU modulates the LuxS/AI-2 QS system by targeting thyA . In vivo experiments further validate the therapeutic potential of 5-FU, showcasing a significant reduction in bacterial load and mitigation of tissue damage in a mouse model. In conclusion, our investigation unveils 5-FU as a potent disruptor of S. suis ‘s biofilm formation and virulence, offering a promising avenue for the control of this devastating pathogen.
研究领域:
微生物学
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感染病学
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药理学
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产品关联
DOI
高影响因子
VETERINARY MICROBIOLOGY
·
2017
·
IF 2.628
Liying Lai,Jiao Dai,Huanyu Tang,Shouming Zhang,Chunyan Wu,Wancen Qiu,Chengping Lu,Huochun Yao,Hongjie Fan,Zongfu Wu
Streptococcus suis (SS), an important pathogen for pigs, is not only considered as a zoonotic agent for humans, but is also recognized as a major reservoir of antimicrobial resistance contributing to the spread of resistance genes to other pathogenic Streptococcus species. In addition to serotype 2 (SS2), serotype 9 (SS9) is another prevalent serotype isolated from diseased pigs. Although many SS strains have been sequenced, the complete genome of a non-SS2 virulent strain has been unavailable to date. Here, we report the complete genome of GZ0565, a virulent strain of SS9, isolated from a pig with meningitis. Comparative genomic analysis revealed five new putative virulence or antimicrobial resistance-associated genes in strain GZ0565 but not in SS2 virulent strains. These five genes encode a putative triacylglycerol lipase, a TipAS antibiotic-recognition domain protein, a putative TetR family transcriptional repressor, a protein containing a LPXTG domain and a G5 domain, and a type VII secretion system (T7SS) putative substrate (EsxA), respectively. Western blot analysis showed that strain GZ0565 can secrete EsxA. We generated an esxA deletion mutant and showed that EsxA contributes to SS virulence in a mouse infection model. Additionally, the antibiotic resistance gene vanZ SS was identified and expression of vanZ SS conferred resistance to teicoplanin and dalbavancin in Streptococcus agalactiae . We believe this is the first experimental demonstration of the existence of the T7SS putative substrate EsxA and its contribution to bacterial virulence in SS. Together, our results contribute to further understanding of the virulence and antimicrobial resistance characteristics of SS.
研究领域:
微生物学
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分子生物学
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传染病学
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抗菌素耐药性
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基因组学
✓ 已验证
DOI
PubMed
高影响因子
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