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...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 mainly 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 produced mtDNA and ROS under induction,leading to the pyroptosis of endothelial cells.展开更多
Muramidase-released protein(MRP)is now being recognized as a critical indicator of the virulence and pathogenicity of Streptococcus suis(S.suis).However,the identification of viable therapeutics for S.suis infection w...Muramidase-released protein(MRP)is now being recognized as a critical indicator of the virulence and pathogenicity of Streptococcus suis(S.suis).However,the identification of viable therapeutics for S.suis infection was hindered by the absence of an explicit mechanism for MRP-actuated inflammation.Dihydroartemisinin(DhA)is an artemisinin derivative with potential anti-inflammatory activity.The modulatory effect of DhA on the inflammatory response mediated by the virulence factor MRP remains obscure.This research aimed to identify the signaling mechanism by which MRP triggers the innate immune response in mouse spleen and cultured macrophages.With the candidate mechanism in mind,we investigated DhA for its ability to dampen the pro-inflammatory response induced by MRP.The innate immune response in mice was drastically triggered by MRP,manifesting as splenic and systemic inflammation with splenomegaly,immune cell infiltration,and an elevation in pro-inflammatory cytokines.A crucial role for Toll-like receptor 4(TLR4)in coordinating the MRP-mediated inflammatory response via nuclear factor-kappa B(NF-kB)activation was revealed by TLR4 blockade.In addition,NFkB-dependent transducer and activator of transcription 3(STAT3)and mitogen-activated protein kinases(MAPKs)activation was required for the inflammatory signal transduction engendered by MRP.Intriguingly,we observed an alleviation effect of DhA on the MRP-induced immune response,which referred to the suppression of TLR4-mediated actuation of NF-kB-STAT3/MAPK cascades.The inflammatory response elicited by MRP is relevant to TLR4-dependent NF-kB activation,followed by an increase in the activity of STAT3 or MAPKs.DhA mitigates the inflammation process induced by MRP via blocking the TLR4 cascade,highlighting the therapeutic potential of DhA in targeting S.suis infection diseases.展开更多
Respiratory diseases are one of the most important health problems in pig herds. The porcine respiratory disease complex (PRDC) is the term used to describe pneumonic diseases caused by multiple infectious agents that...Respiratory diseases are one of the most important health problems in pig herds. The porcine respiratory disease complex (PRDC) is the term used to describe pneumonic diseases caused by multiple infectious agents that provoke weight loss in animals or death. In the PRDC multiple pathogens (bacteria and/or viruses) work in combination to induce this respiratory disease. Within this complex, Actinobacillus pleuropneumoniae, Streptococcus suis, Pasteurella multocida, Bordetella bronchiseptica, Haemophilus parasuis and Mycoplasma hyopneumoniae are the main bacterial pathogens involved in great economic losses to the swine industry. The aim of this work was to estimate the presence of A. pleuropneumoniae, S. suis, P. multocida, B. bronchiseptica, H. parasuis and M. hyopneumoniae in the upper respiratory tract of pigs in representative swine farms inAguascalientes,Mexico, using PCR technique. The study was performed in 14 swine farms. We obtained a total of 212 nasal swabs. Near 20% of samples were positive for A. pleuropneumoniae (located in the 79% of farms);17% were positive for S. suis (in 86% of farms), of these, 3% were S. suis serovar 2;30% were positive for H. parasuis (93% of farms);23% of the samples to P. multocida (in 79% of farms);and 19% to M. hyopneumoniae (in 64% of farms). B. bronchiseptica was not detected in this study. The results obtained show that bacterial pathogens of PRDC were present in the upper respiratory tract of pigs in all farms studied;therefore, these pathogens are widely disseminated in pig farms of Aguascalientes, Mexico.展开更多
对四川猪链球菌2型(S.suis 2)强毒株05ZYH33溶血素样蛋白(hemolysin-like protein,HLP)编码基因hlp进行序列信息分析、分子克隆表达及溶血活性检测,深入探讨HLP的致病机制.用Blast和Clustal X程序对HLP进行基因同源性分析,用Signal P 4....对四川猪链球菌2型(S.suis 2)强毒株05ZYH33溶血素样蛋白(hemolysin-like protein,HLP)编码基因hlp进行序列信息分析、分子克隆表达及溶血活性检测,深入探讨HLP的致病机制.用Blast和Clustal X程序对HLP进行基因同源性分析,用Signal P 4.1和TMHMM Server 2.0分析HLP氨基酸序列.设计合成hlp引物进行PCR扩增,先后将hlp克隆入p MD-18T载体和p ET30a表达载体中,构建p ET30a::hly原核表达质粒.将重组质粒转化至E.coli BL21中诱导表达,并对重组HLP蛋白进行纯化和溶血活性检测.同源性分析表明HLP与多种具有溶血活性的蛋白相似性较高.氨基酸序列分析发现HLP具有信号肽和跨膜区,且由DUF21、CBS和Cor CHly C 3部分组成.序列测定显示hly片段全长1 335 bp,编码445个氨基酸.重组质粒经诱导表达和纯化后电泳显示,HLP分子量约为70 k Da,具有溶血活性.结果表明,HLP是一个膜结合蛋白,不同于能够分泌到细胞外的溶血素Suilysin.重组HLP具有一定的溶血效价,此可能与致病相关.展开更多
[Objectives]This study aimed to investigate the pathogenicity,growth characteristics and drug resistance of Streptococcus suis type 2.[Methods]Bacterial isolation and identification,biochemical experiments,determinati...[Objectives]This study aimed to investigate the pathogenicity,growth characteristics and drug resistance of Streptococcus suis type 2.[Methods]Bacterial isolation and identification,biochemical experiments,determination of growth curve and correlation curve between OD 600 values and viable counts,drug susceptibility tests,pathogenicity analysis,and histopathological observations were carried out.[Results]The Streptococcus strain isolated from infected pigs was identified as Streptococcus suis type 2,which was named TA01 strain.TA01 strain reached the growth peak at 6-8 h post-incubation,and viable counts gradually declined after 8 h of incubation.The correlation equation between OD 600 values and viable counts is y=24.659 x-1.076 1,R^2=0.996 7.TA01 strain was sensitive to penicillin,erythromycin,florfenicol and oxacillin,and resistant to ciprofloxacin,polymyxin B and clindamycin.According to the results of pathogenicity analysis,all the mice in 3.6×10^9 cfu/mouse group died within 48,and these dead mice exhibited acute pyaemia septica.Based on the Reed-Muench formula,it was calculated that LD 50 of TA01 strain was 1.137×10^8 cfu/mouse.Pathological examination showed obvious blue-stained bacteria clusters,accompanied by neutrophil infiltration.[Conclusions]TA01 strain was a virulent strain of Streptococcus suis type 2.Compared with Streptococcus strains which were isolated and reported in China,TA01 strain exhibited strong virulence and rapid proliferation.展开更多
Streptococcus suis is one of the major pathogens of swine streptococcosis. Among them, the strongest virulence and highest rate of clinical isolation serotype is S. suis serotype 2(SS2). Moreover, SS2 is also an impor...Streptococcus suis is one of the major pathogens of swine streptococcosis. Among them, the strongest virulence and highest rate of clinical isolation serotype is S. suis serotype 2(SS2). Moreover, SS2 is also an important zoonosis pathogen, which caused severe public health issues in China. It has been reported that SS2 has several virulence factors, including muramidase released protein, extracellular factors, capsule, fibronectin-binding protein, enolase, hemolysin, small RNA, biofilm, two-component regulatory systems, STK/STP, etc., whose functions involved in adhesion, anti-phagocytosis, inflammatory pathway activation, invasion, etc. Actually, SS2 has developed a variety of ways to escape from host immune system during evolution. In particularly, capsule could resist phagocytosis through inhibiting sphingosine dependent immune cell recognition, which plays an important role in escaping host inflammation response; moreover, superoxide dismutase encoding by sod A enables SS2 escaping reactive oxygen species(ROS) in host immune cells; besides, binding complement factor h with Fhb could suppress the activation of complement alternative pathway and bactericidal effect. And SS2 could also hinder the formation of neutrophil extracellular traps(NETs) to avoid trapping by swine neutrophils, while host immune globulin could be degraded by Ig A1 hydrolase and Ig M protease. In addition, SS2 could escape host immune defense with the help of multiple transcriptional factors and micro-RNA. So far, the pathogenesis of meningitis, arthritis caused by SS2 infection, is still unclear, and the virulence regulatory mechanism of phosphorylation, micro-RNA need to be further clarified. Importantly, the study of interaction mechanism of pathogen and host contribute to further demonstration the pathogenesis of SS2.展开更多
Antimicrobial resistance is undoubtedly one of the greatest global health threats. The emergence of multidrug-resistant(MDR) Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus(MRSA), vancomyc...Antimicrobial resistance is undoubtedly one of the greatest global health threats. The emergence of multidrug-resistant(MDR) Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus(MRSA), vancomycin-resistant Enterococcus faecium(VRE), and β-lactamase-resistant Streptococcus pneumonia, has severely limited our antibiotic arsenal. Numerous ribosome-targeting antibiotics, especially pleuromutilins, oxazolidinones, and streptogramins, are viewed as promising alternatives against aggressive MDR pathogens. In this study, we identified a new adenosine triphosphate(ATP)-binding cassete(ABC)-F family determinant, srp A, in Streptococcus suis(S. suis) by means of a comparative analysis of the whole-genome sequences of tiamulin(TIA)-resistant and TIA-sensitive bacteria. Functional cloning confirmed that the deduced gene can mediate cross-resistance to pleuromutilins, lincosamides, and streptogramin A in S. suis and S. aureus. A sequence alignment revealed that Srp A shares the highest amino acid identity with Vga(E)(36%) and shows canonical characteristics of ABC-F family members.In Srp A-ribosome docked compounds, the extended loop region of Srp A approaches the valnemulinbinding pocket in the ribosome peptidyl-transferase center and competes with bound valnemulin. A detailed mutational analysis of the loop residues confirmed that this domain is crucial for Srp A activity,as substitutions or truncations of this region affect the efficiency and specificity of antibiotic resistance.Intracellular antibiotics accumulation indicated that Srp A does not act as an efflux pump, while a ribosome binding assay supported the protective effects of Srp A on the ribosome by preventing antibiotic binding as well as displacing bound drugs. These findings clarify the mechanisms underlying resistance to ribosomal antibiotics.展开更多
Streptococcus suis(S. suis) is a Gram-positive zoonotic pathogen. S. suis infection in humans commonly causes meningitis, septicemia, arthritis,and streptococcal toxic shock-like syndrome(STSLS). S. suis has 29 seroty...Streptococcus suis(S. suis) is a Gram-positive zoonotic pathogen. S. suis infection in humans commonly causes meningitis, septicemia, arthritis,and streptococcal toxic shock-like syndrome(STSLS). S. suis has 29 serotypes, of which S. suis serotype 2(SS2) has the highest clinical isolation rate and strongest pathogenicity and causes most S. suis human infections.About 1,000 different sequence types(STs)were identified in S.suis based on multilocus sequence typing(MLST).Among these,STs,ST1,and ST7 belong to serotype 2 and are the major hazards of S.suis.in 1998 and 2005,two cases of SS2 human infection outbreak were reported in Jiangsu and Sichuan,China,causing 14 deaths and 38 deaths,respectively.展开更多
BACKGROUND Streptococcus suis(S.suis)is an anthropozoonotic pathogen that shows clinical manifestations of meningitis,septicemia,and arthritis in infected humans.Nocardia is another type of anthropozoonotic bacteria,w...BACKGROUND Streptococcus suis(S.suis)is an anthropozoonotic pathogen that shows clinical manifestations of meningitis,septicemia,and arthritis in infected humans.Nocardia is another type of anthropozoonotic bacteria,with clinical manifestations of skin,lung,and brain abscesses in infected humans.Few intracranial infections caused by S.suis or Nocardia have been reported.To the best of our knowledge,no study has reported a patient with simultaneous intracranial infection by S.suis and Nocardia.CASE SUMMARY A 66-year-old male presented at Liaocheng People’s Hospital(Liaocheng,Shandong Province,China)reporting dizziness with nausea and vomiting.Metagenomic next-generation sequencing(m NGS)was performed on cerebrospinal fluid for examination,and the patient was diagnosed with suppurative meningitis caused by S.suis infection.He received anti-infection treatment with penicillin sodium and ceftriaxone.The patient’s condition initially improved but then deteriorated.Further m NGS of cerebrospinal fluid revealed both S.suis and Nocardia.Imaging examination revealed a brain abscess.Furthermore,a mixed infection of S.suis and Nocardia was detected in the patient’s central nervous system.The patient was treated with antibiotics and sulfamethoxazole.He was discharged after his condition improved.CONCLUSION This case shows that the disease can be recurrent in patients with intracranial infection of a rare pathogen.The possibility of mixed infection should also be considered,especially in patients treated with immunosuppressive agents.m NGS of cerebrospinal fluid is a supplement to conventional microbial pathogen identification methods.Patients with unknown pathogen diagnosis,early extensive use of antibiotics and infection with rare pathogens can be diagnosed by the combination of conventional methods and m NGS of cerebrospinal fluid.展开更多
In this paper,we developed a mathematical model for Streptococcus suis,which is an epidemic by considering the moisture that affects the infection.The disease is caused by Streptococcus suis infection found in pigs wh...In this paper,we developed a mathematical model for Streptococcus suis,which is an epidemic by considering the moisture that affects the infection.The disease is caused by Streptococcus suis infection found in pigs which can be transmitted to humans.The patients of Streptococcus suis were generally found in adults males and the elderly who contacted pigs or who ate uncooked pork.In human cases,the infection can cause a severe illness and death.This disease has an impact to the financial losses in the swine industry.In the development of models for this disease,we have divided the population into 7 related groups which are susceptible pig compartment,infected pig compartment,quarantined pig compartment,recovered pig compartment,susceptible human compartment,infected human compartment,and recovered human compartment.After that,we use this model and a quarantine strategy to analyze the spread of the infection.In addition,the basic reproduction number R0 is determined by using the next-generation matrix which can analyze the stability of the model.The numerical simulations of the proposed model are illustrated to confirm the results from theorems.The results showed that there is an effect from moisture to the disease transmission.When the moisture increases the disease infection also increases.展开更多
In order to diagnose the diseased pigs in a certain large pig farm in Binzhou City,Shandong Province,the dead piglets with joint swelling were subjected to necroscopy,and the pathogenic bacterium was isolated and iden...In order to diagnose the diseased pigs in a certain large pig farm in Binzhou City,Shandong Province,the dead piglets with joint swelling were subjected to necroscopy,and the pathogenic bacterium was isolated and identified. One Gram-positive Streptococcus was isolated. The strain was subjected to characteristic culture,microscopic examination and molecular biological identification,and resistance detection,animal regression experiment and mouse pathogenicity test were carried out. The results showed that the isolate was identified to be Streptococcus suis serotype 7,which was resistant to multiple drugs; and the pathogenicity test showed that the strain had high pathogenicity to pigs,resulting in neurosis on partial pigs,and the strain had no pathogenicity to Kunming and BALB/c mice but certain pathogenicity to CD1 mice.展开更多
Brucella suis (B. suis) is the major cause of porcine brucellosis. Zoonosis due to B. suis infection associated with transmission by various animal species is reported. Recently an increase in brucellosis associated w...Brucella suis (B. suis) is the major cause of porcine brucellosis. Zoonosis due to B. suis infection associated with transmission by various animal species is reported. Recently an increase in brucellosis associated with feral swine transmitted B. suis infection in humans and hunting dogs is emerging. Reports on B. suis infection in carnivores including dogs is scant. This report gives a brief review of B. suis zoonosis with particular reference to B. suis infection in dogs (carnivores).展开更多
Die Thebais des Statius ist ein umfangreiches lateinisches Epos aus dem1.Jahrhundert v.Chr.mit rund zehntausend Hexametem in zwolfBüchem über den Kampf um Theben.Bei diesem Umfang nimmt es nichtwunder,wenn i...Die Thebais des Statius ist ein umfangreiches lateinisches Epos aus dem1.Jahrhundert v.Chr.mit rund zehntausend Hexametem in zwolfBüchem über den Kampf um Theben.Bei diesem Umfang nimmt es nichtwunder,wenn in die fortlaufende Erzahlung auch Einlagen eingefügt sind,die anderes mythisches Gut zum Inhalt haben.Die Frage stellt sich leicht,ob diese Digressionen das Werk im ganzen bereichern oder es belasten.展开更多
Enolase is a conserved cytoplasmic metalloenzyme existing universally in both eukaryotic and prokaryotic cells.The enzyme can also locate on the cell surface and bind to plasminogen,via which contributing to the mucos...Enolase is a conserved cytoplasmic metalloenzyme existing universally in both eukaryotic and prokaryotic cells.The enzyme can also locate on the cell surface and bind to plasminogen,via which contributing to the mucosal surface localization of the bacterial pathogens and assisting the invasion into the host cells.The functions of the eukaryotic enzymes on the cell surface expression(including T cells,B cells,neutrophils,monocytoes,neuronal cells and epithelial cells)are not known.Streptococcus suis serotype 2(S.suis 2,SS2)is an important zoonotic pathogen which has recently caused two large-scale outbreaks in southern China with severe streptococcal toxic shock syndrome(STSS)never seen before in human sufferers.We recently identified the SS2 enolase as an important protective antigen which could protect mice from fatal S.suis 2 infection.In this study,a 2.4-angstrom structure of the SS2 enolase is solved,revealing an octameric arrangement in the crystal.We further demonstrated that the enzyme exists exclusively as an octamer in solution via a sedimentation assay.These results indicate that the octamer is the biological unit of SS2 enolase at least in vitro and most likely in vivo as well.This is,to our knowledge,the first comprehensive characterization of the SS2 enolase octamer both structurally and biophysically,and the second octamer enolase structure in addition to that of Streptococcus pneumoniae.We also investigated the plasminogen binding property of the SS2 enzyme.展开更多
An outbreak associated with Streptococcus suis infection in humans emerged in Sichuan province, China in 2005. The outbreak is atypical for the apparent large number of human cases, high fatality rate and geographical...An outbreak associated with Streptococcus suis infection in humans emerged in Sichuan province, China in 2005. The outbreak is atypical for the apparent large number of human cases, high fatality rate and geographical spread. To determine whether the bacterium has changed, we compared both human and animal isolates from the Sichuan outbreak with those collected previously within China and in other countries using whole genome PCR scanning (WGPScaning) comparative sequencing of several known virulence factor genes and multilocus sequence typing (MLST) analysis. WGPScanning analysis showed that all primer pairs yielded PCR products of the expected sizes in all four strains tested. The nucleotide sequences of all the detected virulence factor genes are identical in the four strains and MLST results showed that the four isolates studied and reference strain all belonged to the ST1 com-plex. No new genetic changes were found in the genome structure of the isolates from this Sichuan outbreak.展开更多
Summary What is already known on this topic?Streptococcus suis(S.suis)is a zoonotic pathogen causing disease in humans and animals,and the emergence of its increased resistance to antimicrobial agents has become a sig...Summary What is already known on this topic?Streptococcus suis(S.suis)is a zoonotic pathogen causing disease in humans and animals,and the emergence of its increased resistance to antimicrobial agents has become a significant challenge in many countries.展开更多
基金supported by the National Natural Science Foundation of China(U22A20520)the Innovation Team Project of Modern Agricultural Industrial Technology System of Guangdong Province,China(2023KJ119)the Natural Science Foundation Program of Guangdong Province,China(2023A1515012206)。
文摘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 mainly 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 produced mtDNA and ROS under induction,leading to the pyroptosis of endothelial cells.
基金supported by the National Key R&D Program of China(Grant Nos.:2022YFF1100104 and 2022YFF1100102)the National Natural Science Foundation of China(Grant Nos.:31625025,32172749,and 32202701)+1 种基金the 2115 Talent Development Program of China Agricultural University(Grant No.:00109016)the Zhengzhou 1125 Talent Program,China(Grant No.:2016XT016).
文摘Muramidase-released protein(MRP)is now being recognized as a critical indicator of the virulence and pathogenicity of Streptococcus suis(S.suis).However,the identification of viable therapeutics for S.suis infection was hindered by the absence of an explicit mechanism for MRP-actuated inflammation.Dihydroartemisinin(DhA)is an artemisinin derivative with potential anti-inflammatory activity.The modulatory effect of DhA on the inflammatory response mediated by the virulence factor MRP remains obscure.This research aimed to identify the signaling mechanism by which MRP triggers the innate immune response in mouse spleen and cultured macrophages.With the candidate mechanism in mind,we investigated DhA for its ability to dampen the pro-inflammatory response induced by MRP.The innate immune response in mice was drastically triggered by MRP,manifesting as splenic and systemic inflammation with splenomegaly,immune cell infiltration,and an elevation in pro-inflammatory cytokines.A crucial role for Toll-like receptor 4(TLR4)in coordinating the MRP-mediated inflammatory response via nuclear factor-kappa B(NF-kB)activation was revealed by TLR4 blockade.In addition,NFkB-dependent transducer and activator of transcription 3(STAT3)and mitogen-activated protein kinases(MAPKs)activation was required for the inflammatory signal transduction engendered by MRP.Intriguingly,we observed an alleviation effect of DhA on the MRP-induced immune response,which referred to the suppression of TLR4-mediated actuation of NF-kB-STAT3/MAPK cascades.The inflammatory response elicited by MRP is relevant to TLR4-dependent NF-kB activation,followed by an increase in the activity of STAT3 or MAPKs.DhA mitigates the inflammation process induced by MRP via blocking the TLR4 cascade,highlighting the therapeutic potential of DhA in targeting S.suis infection diseases.
文摘Respiratory diseases are one of the most important health problems in pig herds. The porcine respiratory disease complex (PRDC) is the term used to describe pneumonic diseases caused by multiple infectious agents that provoke weight loss in animals or death. In the PRDC multiple pathogens (bacteria and/or viruses) work in combination to induce this respiratory disease. Within this complex, Actinobacillus pleuropneumoniae, Streptococcus suis, Pasteurella multocida, Bordetella bronchiseptica, Haemophilus parasuis and Mycoplasma hyopneumoniae are the main bacterial pathogens involved in great economic losses to the swine industry. The aim of this work was to estimate the presence of A. pleuropneumoniae, S. suis, P. multocida, B. bronchiseptica, H. parasuis and M. hyopneumoniae in the upper respiratory tract of pigs in representative swine farms inAguascalientes,Mexico, using PCR technique. The study was performed in 14 swine farms. We obtained a total of 212 nasal swabs. Near 20% of samples were positive for A. pleuropneumoniae (located in the 79% of farms);17% were positive for S. suis (in 86% of farms), of these, 3% were S. suis serovar 2;30% were positive for H. parasuis (93% of farms);23% of the samples to P. multocida (in 79% of farms);and 19% to M. hyopneumoniae (in 64% of farms). B. bronchiseptica was not detected in this study. The results obtained show that bacterial pathogens of PRDC were present in the upper respiratory tract of pigs in all farms studied;therefore, these pathogens are widely disseminated in pig farms of Aguascalientes, Mexico.
文摘对四川猪链球菌2型(S.suis 2)强毒株05ZYH33溶血素样蛋白(hemolysin-like protein,HLP)编码基因hlp进行序列信息分析、分子克隆表达及溶血活性检测,深入探讨HLP的致病机制.用Blast和Clustal X程序对HLP进行基因同源性分析,用Signal P 4.1和TMHMM Server 2.0分析HLP氨基酸序列.设计合成hlp引物进行PCR扩增,先后将hlp克隆入p MD-18T载体和p ET30a表达载体中,构建p ET30a::hly原核表达质粒.将重组质粒转化至E.coli BL21中诱导表达,并对重组HLP蛋白进行纯化和溶血活性检测.同源性分析表明HLP与多种具有溶血活性的蛋白相似性较高.氨基酸序列分析发现HLP具有信号肽和跨膜区,且由DUF21、CBS和Cor CHly C 3部分组成.序列测定显示hly片段全长1 335 bp,编码445个氨基酸.重组质粒经诱导表达和纯化后电泳显示,HLP分子量约为70 k Da,具有溶血活性.结果表明,HLP是一个膜结合蛋白,不同于能够分泌到细胞外的溶血素Suilysin.重组HLP具有一定的溶血效价,此可能与致病相关.
基金Supported by National Key Basic Research Program of China(973 Program)(2017YFD0500605)
文摘[Objectives]This study aimed to investigate the pathogenicity,growth characteristics and drug resistance of Streptococcus suis type 2.[Methods]Bacterial isolation and identification,biochemical experiments,determination of growth curve and correlation curve between OD 600 values and viable counts,drug susceptibility tests,pathogenicity analysis,and histopathological observations were carried out.[Results]The Streptococcus strain isolated from infected pigs was identified as Streptococcus suis type 2,which was named TA01 strain.TA01 strain reached the growth peak at 6-8 h post-incubation,and viable counts gradually declined after 8 h of incubation.The correlation equation between OD 600 values and viable counts is y=24.659 x-1.076 1,R^2=0.996 7.TA01 strain was sensitive to penicillin,erythromycin,florfenicol and oxacillin,and resistant to ciprofloxacin,polymyxin B and clindamycin.According to the results of pathogenicity analysis,all the mice in 3.6×10^9 cfu/mouse group died within 48,and these dead mice exhibited acute pyaemia septica.Based on the Reed-Muench formula,it was calculated that LD 50 of TA01 strain was 1.137×10^8 cfu/mouse.Pathological examination showed obvious blue-stained bacteria clusters,accompanied by neutrophil infiltration.[Conclusions]TA01 strain was a virulent strain of Streptococcus suis type 2.Compared with Streptococcus strains which were isolated and reported in China,TA01 strain exhibited strong virulence and rapid proliferation.
基金supported by the National Key R&D Program of China (2017YFD0500203)the National Transgenic Major Program of China (2014ZX0800946B)+3 种基金the National NaturalScience Foundation of China (31672574)the Special Fund for Agro-scientific Research in the Public Interest, China (201403054)the Jiangsu Agricultural Science and Technology Innovation Fund, China ([CX (16) 1028])the Priority Academic Program Development of Jiangsu Higher Education Institutions, China (PAPD)
文摘Streptococcus suis is one of the major pathogens of swine streptococcosis. Among them, the strongest virulence and highest rate of clinical isolation serotype is S. suis serotype 2(SS2). Moreover, SS2 is also an important zoonosis pathogen, which caused severe public health issues in China. It has been reported that SS2 has several virulence factors, including muramidase released protein, extracellular factors, capsule, fibronectin-binding protein, enolase, hemolysin, small RNA, biofilm, two-component regulatory systems, STK/STP, etc., whose functions involved in adhesion, anti-phagocytosis, inflammatory pathway activation, invasion, etc. Actually, SS2 has developed a variety of ways to escape from host immune system during evolution. In particularly, capsule could resist phagocytosis through inhibiting sphingosine dependent immune cell recognition, which plays an important role in escaping host inflammation response; moreover, superoxide dismutase encoding by sod A enables SS2 escaping reactive oxygen species(ROS) in host immune cells; besides, binding complement factor h with Fhb could suppress the activation of complement alternative pathway and bactericidal effect. And SS2 could also hinder the formation of neutrophil extracellular traps(NETs) to avoid trapping by swine neutrophils, while host immune globulin could be degraded by Ig A1 hydrolase and Ig M protease. In addition, SS2 could escape host immune defense with the help of multiple transcriptional factors and micro-RNA. So far, the pathogenesis of meningitis, arthritis caused by SS2 infection, is still unclear, and the virulence regulatory mechanism of phosphorylation, micro-RNA need to be further clarified. Importantly, the study of interaction mechanism of pathogen and host contribute to further demonstration the pathogenesis of SS2.
基金supported by grants from the National Key Research and Development Program of China(2016YFD0501304 and 2016YFD0501305)supported by the grants from the National Natural Science Foundation of China (31722057)
文摘Antimicrobial resistance is undoubtedly one of the greatest global health threats. The emergence of multidrug-resistant(MDR) Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus(MRSA), vancomycin-resistant Enterococcus faecium(VRE), and β-lactamase-resistant Streptococcus pneumonia, has severely limited our antibiotic arsenal. Numerous ribosome-targeting antibiotics, especially pleuromutilins, oxazolidinones, and streptogramins, are viewed as promising alternatives against aggressive MDR pathogens. In this study, we identified a new adenosine triphosphate(ATP)-binding cassete(ABC)-F family determinant, srp A, in Streptococcus suis(S. suis) by means of a comparative analysis of the whole-genome sequences of tiamulin(TIA)-resistant and TIA-sensitive bacteria. Functional cloning confirmed that the deduced gene can mediate cross-resistance to pleuromutilins, lincosamides, and streptogramin A in S. suis and S. aureus. A sequence alignment revealed that Srp A shares the highest amino acid identity with Vga(E)(36%) and shows canonical characteristics of ABC-F family members.In Srp A-ribosome docked compounds, the extended loop region of Srp A approaches the valnemulinbinding pocket in the ribosome peptidyl-transferase center and competes with bound valnemulin. A detailed mutational analysis of the loop residues confirmed that this domain is crucial for Srp A activity,as substitutions or truncations of this region affect the efficiency and specificity of antibiotic resistance.Intracellular antibiotics accumulation indicated that Srp A does not act as an efflux pump, while a ribosome binding assay supported the protective effects of Srp A on the ribosome by preventing antibiotic binding as well as displacing bound drugs. These findings clarify the mechanisms underlying resistance to ribosomal antibiotics.
基金supported by the National Natural Science Foundation of China [82172332]Gusu health youth talent of Suzhou [GSWS2019039,GSWS2020030]+2 种基金the Science and Technology Program of Suzhou [SKY2021007]Discipline Construction of The Second Affiliated Hospital of Soochow University [XKTJ-TD202001]Postgraduate Research&Practice Innovation Program of Jiangsu Province
文摘Streptococcus suis(S. suis) is a Gram-positive zoonotic pathogen. S. suis infection in humans commonly causes meningitis, septicemia, arthritis,and streptococcal toxic shock-like syndrome(STSLS). S. suis has 29 serotypes, of which S. suis serotype 2(SS2) has the highest clinical isolation rate and strongest pathogenicity and causes most S. suis human infections.About 1,000 different sequence types(STs)were identified in S.suis based on multilocus sequence typing(MLST).Among these,STs,ST1,and ST7 belong to serotype 2 and are the major hazards of S.suis.in 1998 and 2005,two cases of SS2 human infection outbreak were reported in Jiangsu and Sichuan,China,causing 14 deaths and 38 deaths,respectively.
文摘BACKGROUND Streptococcus suis(S.suis)is an anthropozoonotic pathogen that shows clinical manifestations of meningitis,septicemia,and arthritis in infected humans.Nocardia is another type of anthropozoonotic bacteria,with clinical manifestations of skin,lung,and brain abscesses in infected humans.Few intracranial infections caused by S.suis or Nocardia have been reported.To the best of our knowledge,no study has reported a patient with simultaneous intracranial infection by S.suis and Nocardia.CASE SUMMARY A 66-year-old male presented at Liaocheng People’s Hospital(Liaocheng,Shandong Province,China)reporting dizziness with nausea and vomiting.Metagenomic next-generation sequencing(m NGS)was performed on cerebrospinal fluid for examination,and the patient was diagnosed with suppurative meningitis caused by S.suis infection.He received anti-infection treatment with penicillin sodium and ceftriaxone.The patient’s condition initially improved but then deteriorated.Further m NGS of cerebrospinal fluid revealed both S.suis and Nocardia.Imaging examination revealed a brain abscess.Furthermore,a mixed infection of S.suis and Nocardia was detected in the patient’s central nervous system.The patient was treated with antibiotics and sulfamethoxazole.He was discharged after his condition improved.CONCLUSION This case shows that the disease can be recurrent in patients with intracranial infection of a rare pathogen.The possibility of mixed infection should also be considered,especially in patients treated with immunosuppressive agents.m NGS of cerebrospinal fluid is a supplement to conventional microbial pathogen identification methods.Patients with unknown pathogen diagnosis,early extensive use of antibiotics and infection with rare pathogens can be diagnosed by the combination of conventional methods and m NGS of cerebrospinal fluid.
文摘In this paper,we developed a mathematical model for Streptococcus suis,which is an epidemic by considering the moisture that affects the infection.The disease is caused by Streptococcus suis infection found in pigs which can be transmitted to humans.The patients of Streptococcus suis were generally found in adults males and the elderly who contacted pigs or who ate uncooked pork.In human cases,the infection can cause a severe illness and death.This disease has an impact to the financial losses in the swine industry.In the development of models for this disease,we have divided the population into 7 related groups which are susceptible pig compartment,infected pig compartment,quarantined pig compartment,recovered pig compartment,susceptible human compartment,infected human compartment,and recovered human compartment.After that,we use this model and a quarantine strategy to analyze the spread of the infection.In addition,the basic reproduction number R0 is determined by using the next-generation matrix which can analyze the stability of the model.The numerical simulations of the proposed model are illustrated to confirm the results from theorems.The results showed that there is an effect from moisture to the disease transmission.When the moisture increases the disease infection also increases.
基金Supported by Natural Science Foundation of Shandong Province(ZR2014CQ009)Binzhou Municipal Science and Technology Project(2013GG0304)
文摘In order to diagnose the diseased pigs in a certain large pig farm in Binzhou City,Shandong Province,the dead piglets with joint swelling were subjected to necroscopy,and the pathogenic bacterium was isolated and identified. One Gram-positive Streptococcus was isolated. The strain was subjected to characteristic culture,microscopic examination and molecular biological identification,and resistance detection,animal regression experiment and mouse pathogenicity test were carried out. The results showed that the isolate was identified to be Streptococcus suis serotype 7,which was resistant to multiple drugs; and the pathogenicity test showed that the strain had high pathogenicity to pigs,resulting in neurosis on partial pigs,and the strain had no pathogenicity to Kunming and BALB/c mice but certain pathogenicity to CD1 mice.
文摘Brucella suis (B. suis) is the major cause of porcine brucellosis. Zoonosis due to B. suis infection associated with transmission by various animal species is reported. Recently an increase in brucellosis associated with feral swine transmitted B. suis infection in humans and hunting dogs is emerging. Reports on B. suis infection in carnivores including dogs is scant. This report gives a brief review of B. suis zoonosis with particular reference to B. suis infection in dogs (carnivores).
文摘Die Thebais des Statius ist ein umfangreiches lateinisches Epos aus dem1.Jahrhundert v.Chr.mit rund zehntausend Hexametem in zwolfBüchem über den Kampf um Theben.Bei diesem Umfang nimmt es nichtwunder,wenn in die fortlaufende Erzahlung auch Einlagen eingefügt sind,die anderes mythisches Gut zum Inhalt haben.Die Frage stellt sich leicht,ob diese Digressionen das Werk im ganzen bereichern oder es belasten.
基金supported by National Natural Science Foundation of China(NSFC)a leading principal investigator of the NSFC Innovative Research Group(Grant No.81021003).
文摘Enolase is a conserved cytoplasmic metalloenzyme existing universally in both eukaryotic and prokaryotic cells.The enzyme can also locate on the cell surface and bind to plasminogen,via which contributing to the mucosal surface localization of the bacterial pathogens and assisting the invasion into the host cells.The functions of the eukaryotic enzymes on the cell surface expression(including T cells,B cells,neutrophils,monocytoes,neuronal cells and epithelial cells)are not known.Streptococcus suis serotype 2(S.suis 2,SS2)is an important zoonotic pathogen which has recently caused two large-scale outbreaks in southern China with severe streptococcal toxic shock syndrome(STSS)never seen before in human sufferers.We recently identified the SS2 enolase as an important protective antigen which could protect mice from fatal S.suis 2 infection.In this study,a 2.4-angstrom structure of the SS2 enolase is solved,revealing an octameric arrangement in the crystal.We further demonstrated that the enzyme exists exclusively as an octamer in solution via a sedimentation assay.These results indicate that the octamer is the biological unit of SS2 enolase at least in vitro and most likely in vivo as well.This is,to our knowledge,the first comprehensive characterization of the SS2 enolase octamer both structurally and biophysically,and the second octamer enolase structure in addition to that of Streptococcus pneumoniae.We also investigated the plasminogen binding property of the SS2 enzyme.
基金Supported by the National Key Technologies Research and Development Program (Grant No. 2005BA711A09)from the Ministry of Science and Technology of China
文摘An outbreak associated with Streptococcus suis infection in humans emerged in Sichuan province, China in 2005. The outbreak is atypical for the apparent large number of human cases, high fatality rate and geographical spread. To determine whether the bacterium has changed, we compared both human and animal isolates from the Sichuan outbreak with those collected previously within China and in other countries using whole genome PCR scanning (WGPScaning) comparative sequencing of several known virulence factor genes and multilocus sequence typing (MLST) analysis. WGPScanning analysis showed that all primer pairs yielded PCR products of the expected sizes in all four strains tested. The nucleotide sequences of all the detected virulence factor genes are identical in the four strains and MLST results showed that the four isolates studied and reference strain all belonged to the ST1 com-plex. No new genetic changes were found in the genome structure of the isolates from this Sichuan outbreak.
基金Supported by the National Key Research and Development Program of China(2017YFC 1601501 and 2016YFD0501305)Key Research and Development Program of Shandong Province(2019JZZY010719).
文摘Summary What is already known on this topic?Streptococcus suis(S.suis)is a zoonotic pathogen causing disease in humans and animals,and the emergence of its increased resistance to antimicrobial agents has become a significant challenge in many countries.
