Ebola virus disease reemerged in Western Africa in 2014.Chinese Center for Disease Control and Prevention dispatched the first Ebola virus(EBOV)detection team to run newly established Sierra Leone-China Friendship B...Ebola virus disease reemerged in Western Africa in 2014.Chinese Center for Disease Control and Prevention dispatched the first Ebola virus(EBOV)detection team to run newly established Sierra Leone-China Friendship Biological Safety Laboratory.The aims of study were to understand epidemiology,clinical manifestations and survival time of EBOV in patient's blood.A total of 913specimens were tested between March 11 and April20, 2015. EBOV positivity occurred in 7.37% of the blood and 0.53% in throat swabs.展开更多
Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been deve...Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucleotides and RNA interference) approaches. In addition, immune response-based strategies (dendritic cell- and T cell-based therapy) are also under investigation in tumor gene therapy. This review highlights the progress and recent developments in gene delivery systems, therapeutic strategies, and possible clinical directions for gene therapy.展开更多
Objective Fatal familial insomnia (FFI) is an autosomal dominant prion disease characterized clinically by inattention, sleep loss, dysautonomia, and motor signs. This study is aimed to investigate clinical and fami...Objective Fatal familial insomnia (FFI) is an autosomal dominant prion disease characterized clinically by inattention, sleep loss, dysautonomia, and motor signs. This study is aimed to investigate clinical and familial characteristics often Chinese Patients with FFI. Methods We identified ten FFI cases from the surveillance network for Creutafeldt- Jakob disease (CJD) in China.Final diagnosis of FFI cases was made in accordance with the WHO criteria for CJD.The main clinical features and family histories of these ten FFI cases were analyzed. Results The median age of ten cases at onset was 38 years (from 19 to 55). The foremost symptoms seemed to be various, including sleep disturbances, vision disorder, dizziness and anorexia. Sleep disturbances appeared in all cases and lasted in the whole clinical courses. Progressive sympathetic symptoms, memory loss, movement disturbances, myoclonus and hypertension were also frequently observed. The median duration of the disease was 9.5 months. EEG and MRI did not figure out special abnormality. 14-3-3 protein in CSF was positive in five out of eight tested patients. Clear family histories were identified in 8 patients. Conclusion The data from our study confirm that the Chinese FFI cases have similar clinical characteristics as that of the Caucasian cases. Compared with other genetic CJD associated mutations, the genetic frequencies of D178N in PRNP are apparently high among the Chinese cases.展开更多
Lipolytic enzymes, including esterases and lipases, represent a group of hydrolases that catalyze the cleavage and formation of ester bonds. A novel esterase gene, scsEst01, was cloned from a South China Sea sediment ...Lipolytic enzymes, including esterases and lipases, represent a group of hydrolases that catalyze the cleavage and formation of ester bonds. A novel esterase gene, scsEst01, was cloned from a South China Sea sediment metagenome. The scsEst01 gene consisted of 921 bp encoding 307 amino acid residues. The predicted amino acid sequence shared less than 90% identity with other lipolytic enzymes in the NCBI nonredundant protein database. Scs Est01 was successfully co-expressed in E scherichia coli BL21(DE3) with chaperones(dnaK-dna J-grp E) to prevent the formation of inclusion bodies. The recombinant protein was purified on an immobilized metal ion affinity column containing chelating Sepharose charged with Ni2 +. The enzyme was characterized using p-nitrophenol butyrate as a substrate. Scs Est01 had the highest lipolytic activity at 35℃ and p H 8.0, indicative of a meso-thermophilic alkaline esterase. Scs Est01 was thermostable at 20℃. The lipolytic activity of scs Est01 was strongly increased by Fe2 +, Mn 2+ and 1% Tween 80 or Tween 20.展开更多
The human gut microbiome has primarily been studied through the use of fecal samples,a practice that has generated vital knowledge on the composition and functional capacities of gastrointestinal microbial communities...The human gut microbiome has primarily been studied through the use of fecal samples,a practice that has generated vital knowledge on the composition and functional capacities of gastrointestinal microbial communities.However,this reliance on fecal materials limits the investigation of microbial dynamics in other locations along the gastrointestinal tract(in situ),and the infrequent availability of fecal samples prevents analysis at finer temporal scales(e.g.,hours).In our study,we utilized colonic transendoscopic enteral tubing,a technology originally developed for fecal microbiota transplantation,to sample the ileocecal microbiome twice daily;metagenomic and metatranscriptomic analyses were then conducted on these samples.A total of 43 ileocecal and 28 urine and fecal samples were collected from five healthy volunteers.The ileocecal and fecal microbiomes,as profiled in the five volunteers,were found to be similar in metagenomic profiling,yet their active genes(metatranscriptome)were found to be highly distinct.Both microbiomes were perturbed after laxative exposure;over time,they exhibited reduced dissimilarity to their pre-treatment state,thereby demonstrating resilience as an innate property of the gut microbiome,although they did not fully recover within our observation time window.Sampling of the ileocecal microbiome during the day and at night revealed the existence of diurnal rhythms in a series of bacterial species and functional pathways,particularly those related to short-chain fatty acid production,such as Propionibacterium acnes and coenzyme A biosynthesis Ⅱ.Autocorrelation analysis and fluctuations decomposition further indicated the significant periodicity of the diurnal oscillations.Metabolomic profiling in the fecal and urine samples mirrored the perturbance and recovery in the gut microbiome,indicating the crucial contribution of the gut microbiome to many key metabolites involved in host health.This study provides novel insights into the human gut microbiome and its inner resilience and diurnal rhythms,as well as the potential consequences of these to the host.展开更多
Objective To establish Surface-enhanced Raman Spectroscopy(SERS) can be used as a rapid and reliable method to distinguish virulent strain and mild strain of L. pneumophila. Methods We isolated and characterized of ...Objective To establish Surface-enhanced Raman Spectroscopy(SERS) can be used as a rapid and reliable method to distinguish virulent strain and mild strain of L. pneumophila. Methods We isolated and characterized of bacterial strains from ATCC and water samples strains, while we analyzed data from SERS technology using gold nanoparticles as a base and cell infections were employed to rapidly detect L. pneumophila strains. Origin 8.0 was used to collect Raman spectra, smooth and homogenize data, and to contrast spectra. Principal component analysis(PCA) was conducted to discriminate differences between groups using the multivariate analysis package Py Chem 3.0.5. Results Our results indicated that the peaks of high virulence strains reached ≥4000. This criterion was verified by subsequent cell experiments. In addition, we also conducted SERS rapid identification on the virulence of several collected clinical strains and obtained accurate results. Conclusion The present study indicates that the established SERS protocol can be used as a rapid and reliable method to distinguish virulent and mildly virulent strains of L. pneumophila, which can be further used in clinical samples.展开更多
Due to their inability to generate a complete immune response, mice knockout for type I interferon (IFN) receptors (Ifnar-/-) are more susceptible to viral infections, and are thus commonly used for pathogenesis s...Due to their inability to generate a complete immune response, mice knockout for type I interferon (IFN) receptors (Ifnar-/-) are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.展开更多
Recent technological advancements and developments have led to a dramatic increase in the amount of high-dimensional data and thus have increased the demand for proper and efficient multivariate regression methods.Num...Recent technological advancements and developments have led to a dramatic increase in the amount of high-dimensional data and thus have increased the demand for proper and efficient multivariate regression methods.Numerous traditional multivariate approaches such as principal component analysis have been used broadly in various research areas,including investment analysis,image identification,and population genetic structure analysis.However,these common approaches have the limitations of ignoring the correlations between responses and a low variable selection efficiency.Therefore,in this article,we introduce the reduced rank regression method and its extensions,sparse reduced rank regression and subspace assisted regression with row sparsity,which hold potential to meet the above demands and thus improve the interpretability of regression models.We conducted a simulation study to evaluate their performance and compared them with several other variable selection methods.For different application scenarios,we also provide selection suggestions based on predictive ability and variable selection accuracy.Finally,to demonstrate the practical value of these methods in the field of microbiome research,we applied our chosen method to real population-level microbiome data,the results of which validated our method.Our method extensions provide valuable guidelines for future omics research,especially with respect to multivariate regression,and could pave the way for novel discoveries in microbiome and related research fields.展开更多
The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previo...The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs (MARV/Ang- GA). Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD50 was calculated to be 1.1x10-1 TCID50 (median tissue culture infective dose). Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.展开更多
Although carbapenem use is prohibited in animals in China,carbapenem-resistant Escherichia coli(CREC),especially New Delhi metallo-β-lactamase(NDM)-producing strains,are widely prevalent in foodproducing animals.At p...Although carbapenem use is prohibited in animals in China,carbapenem-resistant Escherichia coli(CREC),especially New Delhi metallo-β-lactamase(NDM)-producing strains,are widely prevalent in foodproducing animals.At present,the impact of livestock-associated CREC strains on human populations at the national level is unknown.Here,we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence.We also ascertain the blaNDMand blaKPCabundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin.Overall,631/29799(2.1%)clinical Escherichia coli(E.coli)isolates were identified as CREC.Multivariable analysis revealed that being male,an age below 1,an age between 13 and 18,provinces with greater chicken production,and provinces with higher pig production were associated with higher odds of CREC infection.In general,73.8%(n=45/61)of pig farms and 62.2%(n=28/45)of chicken farms had a blaNDMabundance of 1×10^(-5)to 1×10^(-3)and 1×10^(-3)to 1×10^(-2),respectively.Among all the Chinese NDM-positive E.coli(n=463)available at the National Center for Biotechnology Information(NCBI),the genomic analysis revealed that blaNDM-5and Inc X3 were the predominant carbapenemase gene-plasmid combination,while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels.All the findings suggest frequent CREC transmission between humans and animals,indicating that further discussions on the use of antibiotics in animals and humans are needed,both in China and across the globe.展开更多
Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinician...Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients.Here,we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital,Wuhan,China(development cohort)and externally validated with data from two other centers:141 inpatients from Jinyintan Hospital,Wuhan,China(validation cohort 1)and 432 inpatients from The Third People’s Hospital of Shenzhen,Shenzhen,China(validation cohort 2).The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death.The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90%accuracy across all cohorts.Moreover,the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low,intermediate,or high risk,with an area under the curve(AUC)score of 0.9551.In summary,a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);it has also been validated in independent cohorts.展开更多
Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precurs...Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precursor,are lacking.Here,we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance(NGT);patients with IGT are followed up after 4 years for progression to DM.Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT,DM,and NGT groups.In addition,13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM,including higher levels of Eggerthella unclassified,Coprobacillus unclassified,Clostridium ramosum,L-valine,L-norleucine,and L-isoleucine,and lower levels of Eubacterium eligens,Bacteroides faecis,Lachnospiraceae bacterium 3_1_46FAA,Alistipes senegalensis,Megaspaera elsdenii,Clostridium perfringens,α-linolenic acid,10E,12Z-octadecadienoic acid,and dodecanoic acid.A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM(AUC=0.87).These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.展开更多
Background:Accumulating evidence suggests that metabolic disorders,including type 2 diabetes mellitus(T2DM),can be treated with traditional Chinese medicine formulas,such as the Gegen Qinlian decoction(GQD).This study...Background:Accumulating evidence suggests that metabolic disorders,including type 2 diabetes mellitus(T2DM),can be treated with traditional Chinese medicine formulas,such as the Gegen Qinlian decoction(GQD).This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD.Methods:We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM.During the 12-week intervention,anthropometric measurements and diabetic traits were recorded every 4 weeks.Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing,liquid chromatography-mass spectrometry,and Bio-Plex panels.Results:Anti-diabetic effects were observed in the GQD group in the human trial.Specifically,glycated hemoglobin,fasting plasma glucose,and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group.Additionally,Faecalibacterium was significantly enriched in the GQD group,and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group.Moreover,Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin,fasting plasma glucose,and pro-inflammatory cytokines.Finally,the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzi(DSMZ 17677)in T2DMmousemodel.Conclusions:GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota,alleviating metabolic disorders and the inflammatory state.展开更多
The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the a...The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARSCoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.展开更多
BACKGROUND Fusobacterium nucleatum(F.nucleatum)has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer(CRC),which has attracted broad attention.However,the mechanism...BACKGROUND Fusobacterium nucleatum(F.nucleatum)has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer(CRC),which has attracted broad attention.However,the mechanism by which it is involved in CRC development is not fully understood.AIM To explore its potential causative role in CRC development,we evaluated the colon pathology,mucosa barrier,colon microbiota and host transcriptome profile after F.nucleatum infection in an azoxymethane/dextran sulfate sodium salt(AOM/DSS)mouse model.METHODS Three groups of mice were compared to reveal the differences,i.e.,the control,AOM/DSS-induced CRC and AOM/DSS-FUSO infection groups.RESULTS Both the AOM/DSS and AOM/DSS-FUSO groups exhibited a significantly reduced body weight and increased tumor numbers than the control group,and AOM/DSS mice with F.nucleatum infection showed the highest tumor formation ratio among the three groups.Moreover,the colon pathology was the most serious in the AOM/DSS-FUSO group.We found that the structure of the colon microbiota changed considerably after F.nucleatum infection;striking differences in mucosal microbial population patterns were observed between the AOM/DSS-FUSO and AOM/DSS groups,and inflammation-inducing bacteria were enriched in the mucosal microbiota in the AOM/DSS-FUSO group.By comparing intestinal transcriptomics data from AOM vs AOM/DSSFUSO mice,we showed that transcriptional activity was strongly affected by dysbiosis of the gut microbiota.The most microbiota-sensitive genes were oncogenes in the intestine,and the cyclic adenosine monophosphate signaling pathway,neuroactive ligand–receptor interaction,PPAR signaling pathway,retinol metabolism,mineral absorption and drug metabolism were highly enriched in the AOM/DSS-FUSO group.Additionally,we showed that microbial dysbiosis driven by F.nucleatum infection enriched eight taxa belonging to Proteobacteria,which correlates with increased expression of oncogenic genes.CONCLUSION Our study demonstrated that F.nucleatum infection altered the colon mucosal microbiota by enriching pathogens related to the development of CRC,providing new insights into the role of F.nucleatum in the oncogenic microbial environment of the colon.展开更多
Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases.Meth...Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases.Methods We performed a descriptive study of notifiable infectious diseases among foreigners reported from 2004 to 2017 in China using data from the Chinese National Notifiable Infectious Disease Reporting System(NNIDRIS). Demographic, temporal-spatial distribution were described and analyzed.Results A total of 67,939 cases of 33 different infectious diseases were reported among foreigners.These diseases were seen in 31 provinces of China and originated from 146 countries of the world. The infectious diseases with the highest incidence number were human immunodeficiency virus(HIV) of18,713 cases, hepatitis B(6,461 cases), hand, foot, and mouth disease(6,327 cases). Yunnan province had the highest number of notifiable infectious diseases in foreigners. There were different trends of the major infectious diseases among foreign cases seen in China and varied among provinces.Conclusions This is the first description of the epidemiological characteristic of notifiable infectious diseases among foreigners in China from 2004 to 2017. These data can be used to better inform policymakers about national health priorities for future research and control strategies.展开更多
Gp96, a member of HSP90 family, is a versatile molecular chaperone with various newly-discovered functions, for example to serve as a low affinity, high capacity calcium binding protein, a natural adjuvant for therape...Gp96, a member of HSP90 family, is a versatile molecular chaperone with various newly-discovered functions, for example to serve as a low affinity, high capacity calcium binding protein, a natural adjuvant for therapeutic cancer vaccines, a tumor rejection antigen, an immune regulator to pathological cell death. Its multi-functional and structural characteristics make it also an interesting target to develop antibody-based therapeutics. However, its low immunogenicity to mice, because of its high-sequence similarity among different species, is an obstacle to obtain valuable monoclonal antibodies (MAbs). This is a common problem for any low immunogenic proteins, whose sequences share close identity between mice and other species. Here, a new strategy of priming was employed by swine endogenous full-length gp96 and then boosting by E. coli-system heterologously expressed gp96 N-terminal fragment (N-355) to generate MAbs. Twelve different highly-specific MAbs against swine/human endogenous gp96 were successfully obtained. The binding activities of these MAbs were confirmed by enzyme-linked immunosorbent assay (ELISA), Western blot (WB), immunofluorescence and flow cytometry analysis. This provides some important reagents for further research and potential therapeutics. The methods employed can be used for MAb production of any sequence-highly-conserved proteins between mice and swine/human (or any other species).展开更多
Previous study demonstrated that Ganoderma meroterpene derivative(GMD)increased the abundance of butyrate-producing bacteria in gut and subsequently delivered anti-metabolic disorder effect of host.To specify the key ...Previous study demonstrated that Ganoderma meroterpene derivative(GMD)increased the abundance of butyrate-producing bacteria in gut and subsequently delivered anti-metabolic disorder effect of host.To specify the key commensal bacteria associating with the beneficial effects,we tried to isolate and compare the microbiota from the cecal samples of GMD-and vehicle-treated ob/ob mice,and further identified butyrate-producing bacterial strains.It was found that Faeciroseburia intestinalis was enriched and 11 strains affiliated to F.intestinalis were cultivated from the gut of GMD-treated mice.In vitro assay attested butyrate production by representative strain of F.intestinalis.Oral administration with F.intestinalis further demonstrated its benefits on regulating hyperglycemia and hyperlipidemia,on decreasing plasma lipopolysaccharide(LPS)and inflammation,and on improving hepatic injuries.Treatment with F.intestinalis effectively enhanced the level of gut butyrate,which subsequently ameliorated the intestinal barrier function and activated epithelial PPAR-γ signaling pathway to regulate microbiome homeostasis in gut.Our study demonstrated that the causal relationship between the butyrate-producing bacteria and the GMD's therapeutic effects and confirmed the important function of the butyrate-producing F.intestinalis in maintaining host metabolism homeostasis.展开更多
Secretion systems, macromolecules to pass which can mediate the across cellular membranes, are essential for virulent and genetic material exchange among bacterial species[1]. Type IV secretion system (T4SS) is one ...Secretion systems, macromolecules to pass which can mediate the across cellular membranes, are essential for virulent and genetic material exchange among bacterial species[1]. Type IV secretion system (T4SS) is one of the secretion systems and it usually consists of 12 genes: VirB1, VirB2 ...VirB11, and VirD4[2]. The structure and molecular mechanisms of these genes have been well analyzed in Gram-negative strains[3] and Gram-positive strains were once believed to be lack of T4SS. However, some recent studies revealed that one or more virB/D genes also exist in some kinds of Gram-positive bacteria and play similar role, and form a T4SS-like system[3]. The VirBl-like, VirB4, VirB6, and VirD4 genes were identified in the chromosome of Gram-positive bacterium Streptococcus suis in our previous studies and their role as important mobile elements for horizontal transfer to recipients in an 89 K pathogenicity island (PAl) was demonstrated[45]. However, their structure and molecular mechanisms in other strains, especially in Gram-positive strains, are remained unclear.展开更多
基金supported by a China Mega-Project for Infectious Disease(2011ZX10004-101,2012ZX10004215)Major Program of the National Natural Science Foundation of China(81590763)a SKLID Development Grant(2012SKLID102)
文摘Ebola virus disease reemerged in Western Africa in 2014.Chinese Center for Disease Control and Prevention dispatched the first Ebola virus(EBOV)detection team to run newly established Sierra Leone-China Friendship Biological Safety Laboratory.The aims of study were to understand epidemiology,clinical manifestations and survival time of EBOV in patient's blood.A total of 913specimens were tested between March 11 and April20, 2015. EBOV positivity occurred in 7.37% of the blood and 0.53% in throat swabs.
基金supported by Foundation from Knowl edge Innovation Program in CAS (No. KSCX1-YW-R-10)National Natural Science Foundation of China(No. 30973448)
文摘Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucleotides and RNA interference) approaches. In addition, immune response-based strategies (dendritic cell- and T cell-based therapy) are also under investigation in tumor gene therapy. This review highlights the progress and recent developments in gene delivery systems, therapeutic strategies, and possible clinical directions for gene therapy.
基金This paper is dedicated to the late Professor JS Chiao, who initiated the research in China for rifamycin production employing A. mediterranei more than 30 years ago and who continued the endeavor to resolve the mechanism of the 'nitrate stimulating effect' up to the last breath of his life. This work was supported by the National Natural Science Foundation of China (30830002), the National High Technology Research and Development Program of
China (2007AA021301, 2007AA021503), and the Research Unit Fund of Li Ka Shing Institute of Health Sciences (7103506).
基金supported by China Mega-Project for Infectious Disease(2009ZX10004-101,2008ZX)SKLID Development Grant(2008SKLID102,2011SKLID211)+3 种基金National Basic Research Program of China(973 Program)(2007CB310505)sponsored by the Young Scholar Scientific Research Foundation of China CDC(2012A102)Chinese National Natural Science Foundation Grants 30771914 and 30800975 Institution Technique R&D Grant(2008EG150300)
文摘Objective Fatal familial insomnia (FFI) is an autosomal dominant prion disease characterized clinically by inattention, sleep loss, dysautonomia, and motor signs. This study is aimed to investigate clinical and familial characteristics often Chinese Patients with FFI. Methods We identified ten FFI cases from the surveillance network for Creutafeldt- Jakob disease (CJD) in China.Final diagnosis of FFI cases was made in accordance with the WHO criteria for CJD.The main clinical features and family histories of these ten FFI cases were analyzed. Results The median age of ten cases at onset was 38 years (from 19 to 55). The foremost symptoms seemed to be various, including sleep disturbances, vision disorder, dizziness and anorexia. Sleep disturbances appeared in all cases and lasted in the whole clinical courses. Progressive sympathetic symptoms, memory loss, movement disturbances, myoclonus and hypertension were also frequently observed. The median duration of the disease was 9.5 months. EEG and MRI did not figure out special abnormality. 14-3-3 protein in CSF was positive in five out of eight tested patients. Clear family histories were identified in 8 patients. Conclusion The data from our study confirm that the Chinese FFI cases have similar clinical characteristics as that of the Caucasian cases. Compared with other genetic CJD associated mutations, the genetic frequencies of D178N in PRNP are apparently high among the Chinese cases.
基金Supported by the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDA11030404)the National High Technology Research and Development Program of China(863 Program)(Nos.2012AA092103,2014AA093501,2014AA093505)+1 种基金the Knowledge Innovation Program of Chinese Academy of Sciences(No.KZCX2-YW-JC201)the Open Project Program of Key Laboratory of Marine Bio-Resources Sustainable Utilization,South China Sea Institute of Oceanology,Chinese Academy of Sciences(No.LMB121006)
文摘Lipolytic enzymes, including esterases and lipases, represent a group of hydrolases that catalyze the cleavage and formation of ester bonds. A novel esterase gene, scsEst01, was cloned from a South China Sea sediment metagenome. The scsEst01 gene consisted of 921 bp encoding 307 amino acid residues. The predicted amino acid sequence shared less than 90% identity with other lipolytic enzymes in the NCBI nonredundant protein database. Scs Est01 was successfully co-expressed in E scherichia coli BL21(DE3) with chaperones(dnaK-dna J-grp E) to prevent the formation of inclusion bodies. The recombinant protein was purified on an immobilized metal ion affinity column containing chelating Sepharose charged with Ni2 +. The enzyme was characterized using p-nitrophenol butyrate as a substrate. Scs Est01 had the highest lipolytic activity at 35℃ and p H 8.0, indicative of a meso-thermophilic alkaline esterase. Scs Est01 was thermostable at 20℃. The lipolytic activity of scs Est01 was strongly increased by Fe2 +, Mn 2+ and 1% Tween 80 or Tween 20.
基金supported by the National Key Research and Development Program of China(2018YFC2000500)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29020000)+2 种基金the National Natural Science Foundation of China(31771481,91857101,and 81873548)the Primary Research&Development Plan of Jiangsu Province(BE2018751)the Jiangsu Provincial Medical Innovation Team(F.Zhang)。
文摘The human gut microbiome has primarily been studied through the use of fecal samples,a practice that has generated vital knowledge on the composition and functional capacities of gastrointestinal microbial communities.However,this reliance on fecal materials limits the investigation of microbial dynamics in other locations along the gastrointestinal tract(in situ),and the infrequent availability of fecal samples prevents analysis at finer temporal scales(e.g.,hours).In our study,we utilized colonic transendoscopic enteral tubing,a technology originally developed for fecal microbiota transplantation,to sample the ileocecal microbiome twice daily;metagenomic and metatranscriptomic analyses were then conducted on these samples.A total of 43 ileocecal and 28 urine and fecal samples were collected from five healthy volunteers.The ileocecal and fecal microbiomes,as profiled in the five volunteers,were found to be similar in metagenomic profiling,yet their active genes(metatranscriptome)were found to be highly distinct.Both microbiomes were perturbed after laxative exposure;over time,they exhibited reduced dissimilarity to their pre-treatment state,thereby demonstrating resilience as an innate property of the gut microbiome,although they did not fully recover within our observation time window.Sampling of the ileocecal microbiome during the day and at night revealed the existence of diurnal rhythms in a series of bacterial species and functional pathways,particularly those related to short-chain fatty acid production,such as Propionibacterium acnes and coenzyme A biosynthesis Ⅱ.Autocorrelation analysis and fluctuations decomposition further indicated the significant periodicity of the diurnal oscillations.Metabolomic profiling in the fecal and urine samples mirrored the perturbance and recovery in the gut microbiome,indicating the crucial contribution of the gut microbiome to many key metabolites involved in host health.This study provides novel insights into the human gut microbiome and its inner resilience and diurnal rhythms,as well as the potential consequences of these to the host.
基金supported by National Key Technologies Research and Development Program of China(2013ZX10004-610)China Ministry of Science and Technology(MOST)Project 973(2012CB955501)WL is a principal investigator of the NSFC Innovative Research Group(Grant No.81321063)
文摘Objective To establish Surface-enhanced Raman Spectroscopy(SERS) can be used as a rapid and reliable method to distinguish virulent strain and mild strain of L. pneumophila. Methods We isolated and characterized of bacterial strains from ATCC and water samples strains, while we analyzed data from SERS technology using gold nanoparticles as a base and cell infections were employed to rapidly detect L. pneumophila strains. Origin 8.0 was used to collect Raman spectra, smooth and homogenize data, and to contrast spectra. Principal component analysis(PCA) was conducted to discriminate differences between groups using the multivariate analysis package Py Chem 3.0.5. Results Our results indicated that the peaks of high virulence strains reached ≥4000. This criterion was verified by subsequent cell experiments. In addition, we also conducted SERS rapid identification on the virulence of several collected clinical strains and obtained accurate results. Conclusion The present study indicates that the established SERS protocol can be used as a rapid and reliable method to distinguish virulent and mildly virulent strains of L. pneumophila, which can be further used in clinical samples.
基金supported by the National Natural Science Foundation of China International Cooperation and Exchange Program(8161101193)the National Science and Technology Major Project(2016ZX10004222)to G.Wong
文摘Due to their inability to generate a complete immune response, mice knockout for type I interferon (IFN) receptors (Ifnar-/-) are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.
基金the National Key Research and Development Program of China(2018YFC2000500)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29020000)+1 种基金the National Natural Science Foundation of China(31771481 and 91857101)the Key Research Program of the Chinese Academy of Sciences(KFZD-SW-219),“China Microbiome Initiative.”。
文摘Recent technological advancements and developments have led to a dramatic increase in the amount of high-dimensional data and thus have increased the demand for proper and efficient multivariate regression methods.Numerous traditional multivariate approaches such as principal component analysis have been used broadly in various research areas,including investment analysis,image identification,and population genetic structure analysis.However,these common approaches have the limitations of ignoring the correlations between responses and a low variable selection efficiency.Therefore,in this article,we introduce the reduced rank regression method and its extensions,sparse reduced rank regression and subspace assisted regression with row sparsity,which hold potential to meet the above demands and thus improve the interpretability of regression models.We conducted a simulation study to evaluate their performance and compared them with several other variable selection methods.For different application scenarios,we also provide selection suggestions based on predictive ability and variable selection accuracy.Finally,to demonstrate the practical value of these methods in the field of microbiome research,we applied our chosen method to real population-level microbiome data,the results of which validated our method.Our method extensions provide valuable guidelines for future omics research,especially with respect to multivariate regression,and could pave the way for novel discoveries in microbiome and related research fields.
基金supported by the Public Health Agency of Canada(PHAC)partially supported by the NIH and CIHR grants to X.G.Qiu(U19 AI109762-1 and CIHR-IER-143487,respectively)+1 种基金grants from the National Natural Science Foundation of China International Cooperation and Exchange Program(8161101193)National Science and Technology Major Project(2016ZX10004222)to G.Wong
文摘The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs (MARV/Ang- GA). Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD50 was calculated to be 1.1x10-1 TCID50 (median tissue culture infective dose). Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.
基金supported in part by the grants from National Natural Science Foundation of China(81991535,81861138051,and 81871690)UK MRC DETER-XDR-China-HUB(MR/S013768/1)。
文摘Although carbapenem use is prohibited in animals in China,carbapenem-resistant Escherichia coli(CREC),especially New Delhi metallo-β-lactamase(NDM)-producing strains,are widely prevalent in foodproducing animals.At present,the impact of livestock-associated CREC strains on human populations at the national level is unknown.Here,we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence.We also ascertain the blaNDMand blaKPCabundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin.Overall,631/29799(2.1%)clinical Escherichia coli(E.coli)isolates were identified as CREC.Multivariable analysis revealed that being male,an age below 1,an age between 13 and 18,provinces with greater chicken production,and provinces with higher pig production were associated with higher odds of CREC infection.In general,73.8%(n=45/61)of pig farms and 62.2%(n=28/45)of chicken farms had a blaNDMabundance of 1×10^(-5)to 1×10^(-3)and 1×10^(-3)to 1×10^(-2),respectively.Among all the Chinese NDM-positive E.coli(n=463)available at the National Center for Biotechnology Information(NCBI),the genomic analysis revealed that blaNDM-5and Inc X3 were the predominant carbapenemase gene-plasmid combination,while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels.All the findings suggest frequent CREC transmission between humans and animals,indicating that further discussions on the use of antibiotics in animals and humans are needed,both in China and across the globe.
基金supported by the Special Fund for Novel Coronavirus Pneumonia from the Department of Science and Technology of Hubei Province(2020FCA035)the Fundamental Research Funds for the Central Universities,Huazhong University of Science and Technology(2020kfyXGYJ023).
文摘Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients.Here,we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital,Wuhan,China(development cohort)and externally validated with data from two other centers:141 inpatients from Jinyintan Hospital,Wuhan,China(validation cohort 1)and 432 inpatients from The Third People’s Hospital of Shenzhen,Shenzhen,China(validation cohort 2).The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death.The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90%accuracy across all cohorts.Moreover,the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low,intermediate,or high risk,with an area under the curve(AUC)score of 0.9551.In summary,a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);it has also been validated in independent cohorts.
基金supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202001)the National Natural Science Foundation of China(82104835).
文摘Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precursor,are lacking.Here,we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance(NGT);patients with IGT are followed up after 4 years for progression to DM.Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT,DM,and NGT groups.In addition,13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM,including higher levels of Eggerthella unclassified,Coprobacillus unclassified,Clostridium ramosum,L-valine,L-norleucine,and L-isoleucine,and lower levels of Eubacterium eligens,Bacteroides faecis,Lachnospiraceae bacterium 3_1_46FAA,Alistipes senegalensis,Megaspaera elsdenii,Clostridium perfringens,α-linolenic acid,10E,12Z-octadecadienoic acid,and dodecanoic acid.A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM(AUC=0.87).These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.
基金supported by the National Natural Science Foundation of China (Grants No.81430097,81973837,82004242,82274343 and 31771481)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (Grant No.ZYYCXTD-D-202001).
文摘Background:Accumulating evidence suggests that metabolic disorders,including type 2 diabetes mellitus(T2DM),can be treated with traditional Chinese medicine formulas,such as the Gegen Qinlian decoction(GQD).This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD.Methods:We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM.During the 12-week intervention,anthropometric measurements and diabetic traits were recorded every 4 weeks.Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing,liquid chromatography-mass spectrometry,and Bio-Plex panels.Results:Anti-diabetic effects were observed in the GQD group in the human trial.Specifically,glycated hemoglobin,fasting plasma glucose,and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group.Additionally,Faecalibacterium was significantly enriched in the GQD group,and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group.Moreover,Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin,fasting plasma glucose,and pro-inflammatory cytokines.Finally,the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzi(DSMZ 17677)in T2DMmousemodel.Conclusions:GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota,alleviating metabolic disorders and the inflammatory state.
文摘The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARSCoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.
基金Supported by National Natural Science Foundation of China,No. 32070116Open Project Program of CAS Key Laboratory of Pathogenic Microbiology and Immunology,No. CASPMI202102
文摘BACKGROUND Fusobacterium nucleatum(F.nucleatum)has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer(CRC),which has attracted broad attention.However,the mechanism by which it is involved in CRC development is not fully understood.AIM To explore its potential causative role in CRC development,we evaluated the colon pathology,mucosa barrier,colon microbiota and host transcriptome profile after F.nucleatum infection in an azoxymethane/dextran sulfate sodium salt(AOM/DSS)mouse model.METHODS Three groups of mice were compared to reveal the differences,i.e.,the control,AOM/DSS-induced CRC and AOM/DSS-FUSO infection groups.RESULTS Both the AOM/DSS and AOM/DSS-FUSO groups exhibited a significantly reduced body weight and increased tumor numbers than the control group,and AOM/DSS mice with F.nucleatum infection showed the highest tumor formation ratio among the three groups.Moreover,the colon pathology was the most serious in the AOM/DSS-FUSO group.We found that the structure of the colon microbiota changed considerably after F.nucleatum infection;striking differences in mucosal microbial population patterns were observed between the AOM/DSS-FUSO and AOM/DSS groups,and inflammation-inducing bacteria were enriched in the mucosal microbiota in the AOM/DSS-FUSO group.By comparing intestinal transcriptomics data from AOM vs AOM/DSSFUSO mice,we showed that transcriptional activity was strongly affected by dysbiosis of the gut microbiota.The most microbiota-sensitive genes were oncogenes in the intestine,and the cyclic adenosine monophosphate signaling pathway,neuroactive ligand–receptor interaction,PPAR signaling pathway,retinol metabolism,mineral absorption and drug metabolism were highly enriched in the AOM/DSS-FUSO group.Additionally,we showed that microbial dysbiosis driven by F.nucleatum infection enriched eight taxa belonging to Proteobacteria,which correlates with increased expression of oncogenic genes.CONCLUSION Our study demonstrated that F.nucleatum infection altered the colon mucosal microbiota by enriching pathogens related to the development of CRC,providing new insights into the role of F.nucleatum in the oncogenic microbial environment of the colon.
基金sponsored by National Science and Technology Major Project No. 2016ZX10004222-001。
文摘Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases.Methods We performed a descriptive study of notifiable infectious diseases among foreigners reported from 2004 to 2017 in China using data from the Chinese National Notifiable Infectious Disease Reporting System(NNIDRIS). Demographic, temporal-spatial distribution were described and analyzed.Results A total of 67,939 cases of 33 different infectious diseases were reported among foreigners.These diseases were seen in 31 provinces of China and originated from 146 countries of the world. The infectious diseases with the highest incidence number were human immunodeficiency virus(HIV) of18,713 cases, hepatitis B(6,461 cases), hand, foot, and mouth disease(6,327 cases). Yunnan province had the highest number of notifiable infectious diseases in foreigners. There were different trends of the major infectious diseases among foreign cases seen in China and varied among provinces.Conclusions This is the first description of the epidemiological characteristic of notifiable infectious diseases among foreigners in China from 2004 to 2017. These data can be used to better inform policymakers about national health priorities for future research and control strategies.
基金Project(31030030) supported by the National Natural Science Foundation of China
文摘Gp96, a member of HSP90 family, is a versatile molecular chaperone with various newly-discovered functions, for example to serve as a low affinity, high capacity calcium binding protein, a natural adjuvant for therapeutic cancer vaccines, a tumor rejection antigen, an immune regulator to pathological cell death. Its multi-functional and structural characteristics make it also an interesting target to develop antibody-based therapeutics. However, its low immunogenicity to mice, because of its high-sequence similarity among different species, is an obstacle to obtain valuable monoclonal antibodies (MAbs). This is a common problem for any low immunogenic proteins, whose sequences share close identity between mice and other species. Here, a new strategy of priming was employed by swine endogenous full-length gp96 and then boosting by E. coli-system heterologously expressed gp96 N-terminal fragment (N-355) to generate MAbs. Twelve different highly-specific MAbs against swine/human endogenous gp96 were successfully obtained. The binding activities of these MAbs were confirmed by enzyme-linked immunosorbent assay (ELISA), Western blot (WB), immunofluorescence and flow cytometry analysis. This provides some important reagents for further research and potential therapeutics. The methods employed can be used for MAb production of any sequence-highly-conserved proteins between mice and swine/human (or any other species).
基金supported by the National Key R&D program of China(2019YFA0905602)the National Natural Science Foundation of China(81773614)the Strategic Priority Research Program of Chinese Academy of Sciences(grant No.XDB 38020300).
文摘Previous study demonstrated that Ganoderma meroterpene derivative(GMD)increased the abundance of butyrate-producing bacteria in gut and subsequently delivered anti-metabolic disorder effect of host.To specify the key commensal bacteria associating with the beneficial effects,we tried to isolate and compare the microbiota from the cecal samples of GMD-and vehicle-treated ob/ob mice,and further identified butyrate-producing bacterial strains.It was found that Faeciroseburia intestinalis was enriched and 11 strains affiliated to F.intestinalis were cultivated from the gut of GMD-treated mice.In vitro assay attested butyrate production by representative strain of F.intestinalis.Oral administration with F.intestinalis further demonstrated its benefits on regulating hyperglycemia and hyperlipidemia,on decreasing plasma lipopolysaccharide(LPS)and inflammation,and on improving hepatic injuries.Treatment with F.intestinalis effectively enhanced the level of gut butyrate,which subsequently ameliorated the intestinal barrier function and activated epithelial PPAR-γ signaling pathway to regulate microbiome homeostasis in gut.Our study demonstrated that the causal relationship between the butyrate-producing bacteria and the GMD's therapeutic effects and confirmed the important function of the butyrate-producing F.intestinalis in maintaining host metabolism homeostasis.
基金supported by the National Natural Science Foundation of China (No. 81201322)the Priority Project on Infectious Disease Control and Prevention 2011ZX10004-001 and 2013ZX10003006-002 by the Chinese Ministry of Science and Technology and the Chinese Ministry of Healththe Foundation of State Key Laboratory for Infectious Disease Prevention and Control (Grand No. 2011SKLID303)
文摘Secretion systems, macromolecules to pass which can mediate the across cellular membranes, are essential for virulent and genetic material exchange among bacterial species[1]. Type IV secretion system (T4SS) is one of the secretion systems and it usually consists of 12 genes: VirB1, VirB2 ...VirB11, and VirD4[2]. The structure and molecular mechanisms of these genes have been well analyzed in Gram-negative strains[3] and Gram-positive strains were once believed to be lack of T4SS. However, some recent studies revealed that one or more virB/D genes also exist in some kinds of Gram-positive bacteria and play similar role, and form a T4SS-like system[3]. The VirBl-like, VirB4, VirB6, and VirD4 genes were identified in the chromosome of Gram-positive bacterium Streptococcus suis in our previous studies and their role as important mobile elements for horizontal transfer to recipients in an 89 K pathogenicity island (PAl) was demonstrated[45]. However, their structure and molecular mechanisms in other strains, especially in Gram-positive strains, are remained unclear.