Bacterial pathogens have evolved various mechanisms to modulate host immune responses for successful infection. In this study, RNA- sequencing technology was used to analyze the responses of human monocytes THP1 to Ye...Bacterial pathogens have evolved various mechanisms to modulate host immune responses for successful infection. In this study, RNA- sequencing technology was used to analyze the responses of human monocytes THP1 to Yersinia pestis infection. Over 6000 genes were differentially expressed over the 12 h infection. Kinetic responses of pathogen recognition receptor signaling pathways, apoptosis, antigen processing, and presentation pathway and coagulation system were analyzed in detail. Among them, RIG-I-like receptor （RLR） signaling pathway, which was established for antiviral defense, was significantly affected. Mice lacking MAVS, the adaptor of the RLR signaling pathway, were less sensitive to infection and exhibited lower IFN-13 production, higher Thl-type cytokines IFN-γ and IL-12 production, and lower Th2-type cytokines IL-4 and IL-13 production in the serum compared with wild-type mice. Moreover, infection of pathogenic bacteria other than E pestis also altered the expression of the RLR pathway, suggesting that the response of RLR pathway to bacterial infection is a universal mechanism.展开更多
Objective LcrV is an important component for the development of a subunit vaccine against plague.To reduce immunosuppressive activity of LcrV,a recombinant LcrV variant lacking amino acids 271 to 326 （rV270） was pre...Objective LcrV is an important component for the development of a subunit vaccine against plague.To reduce immunosuppressive activity of LcrV,a recombinant LcrV variant lacking amino acids 271 to 326 （rV270） was prepared by different methods in this study.Methods A new strategy that produced non-tagged or authentic rV270 protein was designed by insertion of rV270-thrombin-hexahistidine fusion gene into the vector pET24a,or by insertion of hexahistidine-enterokinase-rV270 or hexahistitine-factor Xa-rV270 fusion gene into the vector pET32a.After Co2＋ affinity chromatography,a purification strategy was developed by cleavage of His tag on column,following Sephacryl S-200HR column filtration chromatography.Results Removal of His tag by thrombin,enterokinase and factor Xa displayed a yield of 99.5%,32.4% and 15.3%,respectively.Following Sephacryl S-200HR column filtration chromatography,above 97% purity of rV270 protein was obtained.Purified rV270 that was adsorbed to 25% （v/v） Al（OH）3 adjuvant in phosphate-buffered saline （PBS） induced very high titers of antibody to rV270 in BALB/c mice and protected them （100% survival） against subcutaneous challenge with 106 CFU of Y.pestis virulent strain 141.Conclusion The completely authentic rV270 protein can be prepared by using enterokinase or factor Xa,but they exhibited extremely low cleavage activity to the corresponding recognition site.Thrombin cleavage is an efficient strategy to prepare non-tagged rV270 protein and can be easily operated in a large scale due to its relatively low cost and high cleavage efficacy.The recombinant rV270 can be used as a key component to develop a subunit vaccine of plague.展开更多
Objective To investigate genomic variations of two Chinese Yersinia pestis isolates that were isolated from different plague foci obtained from vaccine strain EV76 from the Yunnan province of China. Methods A microarr...Objective To investigate genomic variations of two Chinese Yersinia pestis isolates that were isolated from different plague foci obtained from vaccine strain EV76 from the Yunnan province of China. Methods A microarray containing 12 000 probes covering the entire genome of seven Yersinie pestis and two Yersinia pseudotuberculosis strains, was used. PCR assays were performed to confirm microarray results. Results The gene variations detected included the absence of five genes related to the synthesis of betaine in both EV76 and another sequenced attenuated strain, KIM D27. Several genes related to phage-related membrane proteins were found to be absent in the Antiqua biovar Yunnan strain, 485, which was isolated from a rodent plague foci. Conclusion These findings provide initial insight into the distinct strains isolated from natural foci, within their genomic context, including Yunnan Y. pestis strains. This information will be used therefore to establish subsequent comparisons of these sequences with published complete genomes of other strains.展开更多
Objective This study is to verify the use of rich BHI medium to substitute synthetic media for gene regulation studies in Yersinia pestis. Methods The transcriptional regulation of rovA by PhoP or via temperature upsh...Objective This study is to verify the use of rich BHI medium to substitute synthetic media for gene regulation studies in Yersinia pestis. Methods The transcriptional regulation of rovA by PhoP or via temperature upshift, and that of pla by CRP were investigated when Y. pestis was cultured in BHI. After cultivation under 26 ~C, and with temperature shifting from 26 to 37 ~C, the wild-type （WT） strain or its phoP or crp null mutant （AphoP or Acrp, respectively） was subject to RNA isolation, and then the promoter activity of rovA or plo in the above strains was detected by the primer extension assay. The rovA promoter-proximal region was cloned into the pRW50 containing a promoterless lacZ gene. The recombinant LacZ reporter plasmid was transformed into WT and AphoP to measure the promoter activity of rovA in these two strains with the ^-Galactosidase enzyme assay system. Results When Y. pestis was cultured in BHI, the transcription of rovA was inhibited by PhoP and upon temperature upshift while that ofpla was stimulated by CRP. Conclusion The rich BHI medium without the need for modification to be introduced into the relevant stimulating conditions （which are essential to triggering relevant gene regulatory cascades）, can be used in lieu of synthetic TMH media to cultivate Y. pestis for gene regulation studies.展开更多
Objective To investigate reciprocal regulation between Fur and two RyhB homologs in Yersinia pestis(Y.pestis),as well as the roles of RyhBs in biofilm formation.Methods Regulatory relationships were assessed by a comb...Objective To investigate reciprocal regulation between Fur and two RyhB homologs in Yersinia pestis(Y.pestis),as well as the roles of RyhBs in biofilm formation.Methods Regulatory relationships were assessed by a combination of colony morphology assay,primer extension,electrophoretic mobility shift assay and DNase I footprinting.Results Fur bound to the promoter-proximal DNA regions of ryhB1 and ryhB2 to repress their transcription,while both RyhB1 and RyhB2 repressed the expression of Fur at the post-transcriptional level.In addition,both RyhB1 and RyhB2 positively regulated Y.pestis biofilm exopolysaccharide(EPS)production and the expression of hmsHFRS and hmsT.Conclusion Fur and the two RyhB homologs exert negative reciprocal regulation,and RyhB homologs have a positive regulatory effect on biofilm formation in Y.pestis.展开更多
The aim of this study is to carry out genotyping of 61 Y. pestts strmns tsolated trom lwarmota baibacina-Spermophilus undulates Plague Focus of Tianshan Mountains in China. Primer pairs targeting the 22 DFRs were desi...The aim of this study is to carry out genotyping of 61 Y. pestts strmns tsolated trom lwarmota baibacina-Spermophilus undulates Plague Focus of Tianshan Mountains in China. Primer pairs targeting the 22 DFRs were designed for detecting the genotypes of 61 strains. As a result, 61 strains of Y. pestis were divided into four genotypes 1, 2, 3, and 4. Genotypes 1, 2 and 3 were found from west part in Northern Tianshan Mountains Plague Focus, but type 1 was only from Nileke county. The type of strains from Aheqi was different from those of Atushi counties in Southern Tianshan Mountains and similar to strains in Northern Tianshan Mountains Plague Focus. The type 4 distributed over Atushi county, which was identical with that of strains from Marmota caudae Plague Focus of the Pamiri Plateau. It is concluded that geonotyping is identical with ecotyping made by Shuli Ji. Tianshan Mountains Plague Focus and Marmota caudae Plague Focus of the Pamiri Plateau have a cross spreading profile.展开更多
Plague is a zoonotic disease caused by the bacterium Yersinia pestis Lehmann and Neumann,1896.Although it is essentially a disease of rodents,plague can also be transmitted to people.Historically,plague has caused mas...Plague is a zoonotic disease caused by the bacterium Yersinia pestis Lehmann and Neumann,1896.Although it is essentially a disease of rodents,plague can also be transmitted to people.Historically,plague has caused mas-sive morbidity and mortality events in human populations,and has recently been classified as a reemerging dis-ease in many parts of the world.This public health threat has led many countries to set up wild and domestic an-imal surveillance programs in an attempt to monitor plague activity that could potentially spill over into human populations.Both China and the USA have plague surveillance programs in place,but the disease dynamics dif-fer in each country.We present data on plague seroprevalence in wildlife and review different approaches for plague surveillance in the 2 countries.The need to better comprehend plague dynamics,combined with the fact that there are still several thousand human plague cases per year,make well-designed wildlife surveillance pro-grams a critical part of both understanding plague risks to humans and preventing disease outbreaks in the future.展开更多
Yersinia pestis is the bacteria that causes plague,one of the deadliest diseases in human history.Three major plague pandemics(the Justinian Plague,the Black Death and the Modern Plague)have been recorded.Each caused ...Yersinia pestis is the bacteria that causes plague,one of the deadliest diseases in human history.Three major plague pandemics(the Justinian Plague,the Black Death and the Modern Plague)have been recorded.Each caused massive fatalities and has become defining events in the time periods in places that were affected.The presence of natural plague foci in rodents across the world is one of the risk factors for human plague.While plague is a relatively rare problem for most countries,more than 90%of plague cases in the world still occur in Africa.This article discusses the threat of Yersinia pestis in the modern world by considering its prevalence and severity of illness it causes,transmission,antibiotic resistance,and its potential as a bioweapon.展开更多
In this study,we designed and engineered a two-component recombinant fusionprotein antigen as a vaccine candidate against the possible biological threat of Yersinia pestis.Therecombinant F1-V protein was formulated wi...In this study,we designed and engineered a two-component recombinant fusionprotein antigen as a vaccine candidate against the possible biological threat of Yersinia pestis.Therecombinant F1-V protein was formulated with Alhydrogel.A four-time injection with a dosage of10,20 and 50 ug/mouse in about two months was adopted for vaccination.Serum antibodies and subclassof T helper cells were measured and analyzed.After the final vaccination,the mice were challenged by141 strain with 25- 600 LD50.In conclusion,the recombinant vaccine was capable of inducingprotective immunity against subcutaneous challenge.The level of serum IgG was supposed to be a mainfactor that affected the final protection of challenge.20 ug recombinant protein could induce anendpoint titre of serum IgG as high as 51200,which was enough to afford 100% protection against 400LD50 virulent 141 challenge.The antibody isotype analysis showed that the vaccine inducedpredominantly an lgG1 rather than lgG2a response.Flow cytometric analysis revealed that Alhydrogelsignificantly helped induce a stronger humoral immunity instead of CTL cellular response.Thesefindings suggested that the plague F1-V subunit vaccine is promising for the next plague vaccine.展开更多
Chinese tongue diagnosis was initially developed to quickly and efficiently diagnose and prescribe medicine, while at the same time allowing the doctor to have minimal contact with the patient. At the time of its comp...Chinese tongue diagnosis was initially developed to quickly and efficiently diagnose and prescribe medicine, while at the same time allowing the doctor to have minimal contact with the patient. At the time of its compiling, the spread of Yersinia pestis, often causing septicaemia and gangrene of the extremities,may have discouraged doctors to come in direct contact with their patients and take the pulse.However, in recent decades, modern developments in the field of traditional Chinese medicine, as well as the spread of antibiotics in conjunction with the advancements of microbiology, have overshadowed the original purpose of this methodology. Nevertheless, the fast approaching post-antibiotic era and the development of artificial intelligence may hold new applications for tongue diagnosis. This article focuses on the historical development of what is the world＇s earliest tongue diagnosis monograph, and discusses the directions that such knowledge may be used in future clinical research.展开更多
The purpose of the paper was to assess the frequency of secondary transmissions of primary pneumonic plague relative to the onset of fever.A simple backcalculation method was employed to estimate the frequency of seco...The purpose of the paper was to assess the frequency of secondary transmissions of primary pneumonic plague relative to the onset of fever.A simple backcalculation method was employed to estimate the frequency of secondary transmissions relative to disease-age.A likelihood-based procedure was taken using observed distributions of the serial interval(n = 177) and incubation period(n = 126).Furthermore,an extended model was developed to account for the survival probability of cases.The simple backcalculation suggested that 31. 0%(95%confidence intervals(CI):11.6,50.4) and 28.0%(95%CI:10.2,45.8) of the total number of secondary transmissions had occurred at second and third days of the disease,respectively,and more than four-fifths of the secondary transmission occurred before the end of third day of disease.The survivorship-adjusted frequency of secondary transmissions was obtained,demonstrating that the infectiousness in later stages of illness was not insignificant and indicates that the obtained frequencies were likely biased on underlying factors including isolation measures.In conclusion,the simple exercise suggests a need to implement countermeasures during pre-clinical stage or immediately after onset.Further information is needed to elucidate the finer details of the disease-age specific infectiousness.展开更多
Plague caused by Yersinia pestis is one of the infectious diseases subject to the International Health Regulations (IHR). Permanent monitoring of the focal plague areas is mandatory in order to enable prompt control m...Plague caused by Yersinia pestis is one of the infectious diseases subject to the International Health Regulations (IHR). Permanent monitoring of the focal plague areas is mandatory in order to enable prompt control measures to prevent the spread of the disease. Therefore, the availability of efficient diagnosis tests is of paramount importance. Here, we describe a loop-mediated isothermal amplification (LAMP)-based procedure for rapid Y. pestis detection. We constructed a set of LAMP primers, which were used in assays to establish the reaction conditions that would lead to the quick visualization of the results by evaluating the test tube with the naked eye. The primers were specifically designed to target the caf1 gene located on pFra/Tox (pMT), a prototypical plasmid of Y. pestis. The LAMP procedure was performed at 65°C for 45 min in a water bath and allowed for the detection of at least 10 pg of bacterial DNA. Due to its simplicity, specificity, sensitivity and rapidity, the LAMP technique is an additional tool that may be implemented in routine plague diagnoses, especially in emergencies.展开更多
Objective:To characterize the case fatality and estimate the symptomatic period of bubonic plague.Methods: Epidemiologic analyses of a previous outbreak of plague in Osaka and Kobe,two major port cities in Japan, from...Objective:To characterize the case fatality and estimate the symptomatic period of bubonic plague.Methods: Epidemiologic analyses of a previous outbreak of plague in Osaka and Kobe,two major port cities in Japan, from 1899-1900 were performed.In addition to date of onset of symptoms,gender,age and the date of death were extracted from the historical data.The time from onset to death(symptomatic period) was fitted to gamma distribution using the maximum likelihood method.Results:Temporal distribution revealed suspected chains of transmission of the primary pneumonic plague at the late stage of the outbreak.The case fatality of bubonic plague without specific treatment was 83.4%,and the mean time from onset to death was estimated as 4.7 days(95%confidence interval;4.0,5.5).Conclusion:Case fatality of bubonic plague without specific treatment was extremely high.The symptomatic period of bubonic plague appeared to be longer than that of pneumonic plague.展开更多
More and more national investments go into the TCM industry in recent years,but few break-throughs have been made in the devel-opment of key theories or technologies.And the lack of innovation remains a problem and hi...More and more national investments go into the TCM industry in recent years,but few break-throughs have been made in the devel-opment of key theories or technologies.And the lack of innovation remains a problem and hinders the growth of the TCM industry.To solve the problem,the Twelfth Five-year Plan for展开更多
Flea-borne transmission is a recent evolutionary adaptation that distinguishes the deadly Yersinia pestis from its progenitor Y.pseudotuberculosis,a mild pathogen transmitted via the food-borne route.Y.pestis synthesi...Flea-borne transmission is a recent evolutionary adaptation that distinguishes the deadly Yersinia pestis from its progenitor Y.pseudotuberculosis,a mild pathogen transmitted via the food-borne route.Y.pestis synthesizes biofilms in the flea gut,which is important for fleaborne transmission.Yersinia biofilms are bacterial colonies surrounded by extracellular matrix primarily containing a homopolymer of N-acetyl-D-glucosamine that are synthesized by a set of specific enzymes.Yersinia biofilm production is tightly regulated at both transcriptional and post-transcriptional levels.All the known structural genes responsible for biofilm production are harbored in both Y.pseudotuberculosis and Y.pestis,but Y.pestis has evolved changes in the regulation of biofilm development,thereby acquiring efficient arthropod-borne transmission.展开更多
Plague,caused by Yersinia pestis,is a flea-borne disease that is endemic in areas throughout the world due to its successful maintenance in a sylvatic cycle,mainly in areas with temperate climates.Burrowing rodents ar...Plague,caused by Yersinia pestis,is a flea-borne disease that is endemic in areas throughout the world due to its successful maintenance in a sylvatic cycle,mainly in areas with temperate climates.Burrowing rodents are thought to play a key role in the enzootic maintenance as well as epizootic outbreaks of plague.In the United States,prairie dogs(Cynomys),rodents(Muridae),and ground squirrels(Spermophilus)are susceptible to infection and are parasitized by fleas that transmit plague.In particular,prairie dogs can experience outbreaks that rapidly spread,which can lead to extirpation of colonies.A number of ecological parameters,including climate,are associated with these epizootics.In this study,we asked whether soil parameters,primarily moisture and temperature,are associated with outbreaks of plague in black-tailed prairie dogs and Gunnison’s prairie dogs in the Western United States,and at what depth these associations were apparent.We collected publicly available county-level information on the occurrence of population declines or colony extirpation,while historical soil data was collected from SCAN and USCRN stations in counties and states where prairie dogs have been located.The analysis suggests that soil moisture at lower depths correlates with colony die-offs,in addition to temperature near the surface,with key differences within the landscape ecology that impact the occurrence of plague.Overall,the model suggests that the burrow environment may play a significant role in the epizootic spread of disease amongst black-tailed and Gunnison’s prairie dogs.展开更多
The epidemiology of Yersinia pestis,the causative agent of plague,involves vectors and reservoirs in its transmission cycle.The passive plague surveillance in Madagascar targets mainly rodent and fleas.However,carnivo...The epidemiology of Yersinia pestis,the causative agent of plague,involves vectors and reservoirs in its transmission cycle.The passive plague surveillance in Madagascar targets mainly rodent and fleas.However,carnivores are routinely surveyed as sentinels of local plague activity in some countries.The aim of this study is to assess the use of domestic dog(Canis familiaris)as sentinel animal for field surveillance of plague in a highly endemic area in Madagascar.Cross-sectional surveys of plague antibody prevalence in C.familiaris were conducted in endemic areas with contrasting histories of plague cases in humans,as well as a plague free area.Rodent capture was done in parallel to evaluate evidence for Y.pestis circulation in the primary reservoirs.In 2 sites,dogs were later re-sampled to examine evidence of seroconversion and antibody persistence.Biological samplings were performed between March 2008 and February 2009.Plague antibody detection was assessed using anti-F1 ELISA.Our study showed a significant difference in dog prevalence rates between plague-endemic and plague-free areas,with no seropositive dogs detected in the plague free area.No correlation was found between rodents and dog prevalence rates,with an absence of seropositive rodents in some area where plague circulation was indicated by seropositive dogs.This is consistent with high mortality rates in rodents following infection.Re-sampling dogs identified individuals seropositive on both occasions,indicating high rates of re-exposure and/or persistence of plague antibodies for at least 9 months.Seroconversion or seropositive juvenile dogs indicated recent local plague circulation.In Madagascar,dog surveillance for plague antibody could be useful to identify plague circulation in new areas or quiescent areas within endemic zones.Within active endemic areas,monitoring of dog populations for seroconversion(negative to positive)or seropositive juvenile dogs could be useful for identifying areas at greatest risk of human outbreaks.展开更多
基金supported by the National Basic Research Program of China(Nos.2012CB518704 and 2013CB910804)the National Natural Science Foundation of China(No.31170122)the Basic Research Programs of Science and Technology Department Foundation of QingHai Province(No.2013-Z-748)
文摘Bacterial pathogens have evolved various mechanisms to modulate host immune responses for successful infection. In this study, RNA- sequencing technology was used to analyze the responses of human monocytes THP1 to Yersinia pestis infection. Over 6000 genes were differentially expressed over the 12 h infection. Kinetic responses of pathogen recognition receptor signaling pathways, apoptosis, antigen processing, and presentation pathway and coagulation system were analyzed in detail. Among them, RIG-I-like receptor （RLR） signaling pathway, which was established for antiviral defense, was significantly affected. Mice lacking MAVS, the adaptor of the RLR signaling pathway, were less sensitive to infection and exhibited lower IFN-13 production, higher Thl-type cytokines IFN-γ and IL-12 production, and lower Th2-type cytokines IL-4 and IL-13 production in the serum compared with wild-type mice. Moreover, infection of pathogenic bacteria other than E pestis also altered the expression of the RLR pathway, suggesting that the response of RLR pathway to bacterial infection is a universal mechanism.
基金supported by the National Key Program for Infectious Diseases of China (2009ZX10004-4001)
文摘Objective LcrV is an important component for the development of a subunit vaccine against plague.To reduce immunosuppressive activity of LcrV,a recombinant LcrV variant lacking amino acids 271 to 326 （rV270） was prepared by different methods in this study.Methods A new strategy that produced non-tagged or authentic rV270 protein was designed by insertion of rV270-thrombin-hexahistidine fusion gene into the vector pET24a,or by insertion of hexahistidine-enterokinase-rV270 or hexahistitine-factor Xa-rV270 fusion gene into the vector pET32a.After Co2＋ affinity chromatography,a purification strategy was developed by cleavage of His tag on column,following Sephacryl S-200HR column filtration chromatography.Results Removal of His tag by thrombin,enterokinase and factor Xa displayed a yield of 99.5%,32.4% and 15.3%,respectively.Following Sephacryl S-200HR column filtration chromatography,above 97% purity of rV270 protein was obtained.Purified rV270 that was adsorbed to 25% （v/v） Al（OH）3 adjuvant in phosphate-buffered saline （PBS） induced very high titers of antibody to rV270 in BALB/c mice and protected them （100% survival） against subcutaneous challenge with 106 CFU of Y.pestis virulent strain 141.Conclusion The completely authentic rV270 protein can be prepared by using enterokinase or factor Xa,but they exhibited extremely low cleavage activity to the corresponding recognition site.Thrombin cleavage is an efficient strategy to prepare non-tagged rV270 protein and can be easily operated in a large scale due to its relatively low cost and high cleavage efficacy.The recombinant rV270 can be used as a key component to develop a subunit vaccine of plague.
基金supported by a grant from the National High Technology Research and Development Program of China (863 Program) (No. 2006AA2Z4A7)a grant from the National Key Program for Infectious Diseases of China (No.2008ZX1004-002)a grant from China Mega-Project for Infectious Disease (No.2011ZX10004-001)
文摘Objective To investigate genomic variations of two Chinese Yersinia pestis isolates that were isolated from different plague foci obtained from vaccine strain EV76 from the Yunnan province of China. Methods A microarray containing 12 000 probes covering the entire genome of seven Yersinie pestis and two Yersinia pseudotuberculosis strains, was used. PCR assays were performed to confirm microarray results. Results The gene variations detected included the absence of five genes related to the synthesis of betaine in both EV76 and another sequenced attenuated strain, KIM D27. Several genes related to phage-related membrane proteins were found to be absent in the Antiqua biovar Yunnan strain, 485, which was isolated from a rodent plague foci. Conclusion These findings provide initial insight into the distinct strains isolated from natural foci, within their genomic context, including Yunnan Y. pestis strains. This information will be used therefore to establish subsequent comparisons of these sequences with published complete genomes of other strains.
基金supported by the National Natural Science Foundation of China (30930001 and 30900823)
文摘Objective This study is to verify the use of rich BHI medium to substitute synthetic media for gene regulation studies in Yersinia pestis. Methods The transcriptional regulation of rovA by PhoP or via temperature upshift, and that of pla by CRP were investigated when Y. pestis was cultured in BHI. After cultivation under 26 ~C, and with temperature shifting from 26 to 37 ~C, the wild-type （WT） strain or its phoP or crp null mutant （AphoP or Acrp, respectively） was subject to RNA isolation, and then the promoter activity of rovA or plo in the above strains was detected by the primer extension assay. The rovA promoter-proximal region was cloned into the pRW50 containing a promoterless lacZ gene. The recombinant LacZ reporter plasmid was transformed into WT and AphoP to measure the promoter activity of rovA in these two strains with the ^-Galactosidase enzyme assay system. Results When Y. pestis was cultured in BHI, the transcription of rovA was inhibited by PhoP and upon temperature upshift while that ofpla was stimulated by CRP. Conclusion The rich BHI medium without the need for modification to be introduced into the relevant stimulating conditions （which are essential to triggering relevant gene regulatory cascades）, can be used in lieu of synthetic TMH media to cultivate Y. pestis for gene regulation studies.
基金supported by the Basic Application Research Project of Science and Technology Department of Qinghai province[2020-ZJ-788]the Key Laboratory of National Health Commission on Plague Control and Prevention[2019PT310004]+1 种基金the Key Laboratory for Plague Prevention and Control of Qinghai Province[p2020-ZJ-Y23]the Qinghai Province High-end Innovative Talents Thousand Talents Program(2019)。
文摘Objective To investigate reciprocal regulation between Fur and two RyhB homologs in Yersinia pestis(Y.pestis),as well as the roles of RyhBs in biofilm formation.Methods Regulatory relationships were assessed by a combination of colony morphology assay,primer extension,electrophoretic mobility shift assay and DNase I footprinting.Results Fur bound to the promoter-proximal DNA regions of ryhB1 and ryhB2 to repress their transcription,while both RyhB1 and RyhB2 repressed the expression of Fur at the post-transcriptional level.In addition,both RyhB1 and RyhB2 positively regulated Y.pestis biofilm exopolysaccharide(EPS)production and the expression of hmsHFRS and hmsT.Conclusion Fur and the two RyhB homologs exert negative reciprocal regulation,and RyhB homologs have a positive regulatory effect on biofilm formation in Y.pestis.
文摘The aim of this study is to carry out genotyping of 61 Y. pestts strmns tsolated trom lwarmota baibacina-Spermophilus undulates Plague Focus of Tianshan Mountains in China. Primer pairs targeting the 22 DFRs were designed for detecting the genotypes of 61 strains. As a result, 61 strains of Y. pestis were divided into four genotypes 1, 2, 3, and 4. Genotypes 1, 2 and 3 were found from west part in Northern Tianshan Mountains Plague Focus, but type 1 was only from Nileke county. The type of strains from Aheqi was different from those of Atushi counties in Southern Tianshan Mountains and similar to strains in Northern Tianshan Mountains Plague Focus. The type 4 distributed over Atushi county, which was identical with that of strains from Marmota caudae Plague Focus of the Pamiri Plateau. It is concluded that geonotyping is identical with ecotyping made by Shuli Ji. Tianshan Mountains Plague Focus and Marmota caudae Plague Focus of the Pamiri Plateau have a cross spreading profile.
文摘Plague is a zoonotic disease caused by the bacterium Yersinia pestis Lehmann and Neumann,1896.Although it is essentially a disease of rodents,plague can also be transmitted to people.Historically,plague has caused mas-sive morbidity and mortality events in human populations,and has recently been classified as a reemerging dis-ease in many parts of the world.This public health threat has led many countries to set up wild and domestic an-imal surveillance programs in an attempt to monitor plague activity that could potentially spill over into human populations.Both China and the USA have plague surveillance programs in place,but the disease dynamics dif-fer in each country.We present data on plague seroprevalence in wildlife and review different approaches for plague surveillance in the 2 countries.The need to better comprehend plague dynamics,combined with the fact that there are still several thousand human plague cases per year,make well-designed wildlife surveillance pro-grams a critical part of both understanding plague risks to humans and preventing disease outbreaks in the future.
文摘Yersinia pestis is the bacteria that causes plague,one of the deadliest diseases in human history.Three major plague pandemics(the Justinian Plague,the Black Death and the Modern Plague)have been recorded.Each caused massive fatalities and has become defining events in the time periods in places that were affected.The presence of natural plague foci in rodents across the world is one of the risk factors for human plague.While plague is a relatively rare problem for most countries,more than 90%of plague cases in the world still occur in Africa.This article discusses the threat of Yersinia pestis in the modern world by considering its prevalence and severity of illness it causes,transmission,antibiotic resistance,and its potential as a bioweapon.
文摘In this study,we designed and engineered a two-component recombinant fusionprotein antigen as a vaccine candidate against the possible biological threat of Yersinia pestis.Therecombinant F1-V protein was formulated with Alhydrogel.A four-time injection with a dosage of10,20 and 50 ug/mouse in about two months was adopted for vaccination.Serum antibodies and subclassof T helper cells were measured and analyzed.After the final vaccination,the mice were challenged by141 strain with 25- 600 LD50.In conclusion,the recombinant vaccine was capable of inducingprotective immunity against subcutaneous challenge.The level of serum IgG was supposed to be a mainfactor that affected the final protection of challenge.20 ug recombinant protein could induce anendpoint titre of serum IgG as high as 51200,which was enough to afford 100% protection against 400LD50 virulent 141 challenge.The antibody isotype analysis showed that the vaccine inducedpredominantly an lgG1 rather than lgG2a response.Flow cytometric analysis revealed that Alhydrogelsignificantly helped induce a stronger humoral immunity instead of CTL cellular response.Thesefindings suggested that the plague F1-V subunit vaccine is promising for the next plague vaccine.
基金Supported by the National Natural Science Foundation(No.81603516)
文摘Chinese tongue diagnosis was initially developed to quickly and efficiently diagnose and prescribe medicine, while at the same time allowing the doctor to have minimal contact with the patient. At the time of its compiling, the spread of Yersinia pestis, often causing septicaemia and gangrene of the extremities,may have discouraged doctors to come in direct contact with their patients and take the pulse.However, in recent decades, modern developments in the field of traditional Chinese medicine, as well as the spread of antibiotics in conjunction with the advancements of microbiology, have overshadowed the original purpose of this methodology. Nevertheless, the fast approaching post-antibiotic era and the development of artificial intelligence may hold new applications for tongue diagnosis. This article focuses on the historical development of what is the world＇s earliest tongue diagnosis monograph, and discusses the directions that such knowledge may be used in future clinical research.
文摘The purpose of the paper was to assess the frequency of secondary transmissions of primary pneumonic plague relative to the onset of fever.A simple backcalculation method was employed to estimate the frequency of secondary transmissions relative to disease-age.A likelihood-based procedure was taken using observed distributions of the serial interval(n = 177) and incubation period(n = 126).Furthermore,an extended model was developed to account for the survival probability of cases.The simple backcalculation suggested that 31. 0%(95%confidence intervals(CI):11.6,50.4) and 28.0%(95%CI:10.2,45.8) of the total number of secondary transmissions had occurred at second and third days of the disease,respectively,and more than four-fifths of the secondary transmission occurred before the end of third day of disease.The survivorship-adjusted frequency of secondary transmissions was obtained,demonstrating that the infectiousness in later stages of illness was not insignificant and indicates that the obtained frequencies were likely biased on underlying factors including isolation measures.In conclusion,the simple exercise suggests a need to implement countermeasures during pre-clinical stage or immediately after onset.Further information is needed to elucidate the finer details of the disease-age specific infectiousness.
文摘Plague caused by Yersinia pestis is one of the infectious diseases subject to the International Health Regulations (IHR). Permanent monitoring of the focal plague areas is mandatory in order to enable prompt control measures to prevent the spread of the disease. Therefore, the availability of efficient diagnosis tests is of paramount importance. Here, we describe a loop-mediated isothermal amplification (LAMP)-based procedure for rapid Y. pestis detection. We constructed a set of LAMP primers, which were used in assays to establish the reaction conditions that would lead to the quick visualization of the results by evaluating the test tube with the naked eye. The primers were specifically designed to target the caf1 gene located on pFra/Tox (pMT), a prototypical plasmid of Y. pestis. The LAMP procedure was performed at 65°C for 45 min in a water bath and allowed for the detection of at least 10 pg of bacterial DNA. Due to its simplicity, specificity, sensitivity and rapidity, the LAMP technique is an additional tool that may be implemented in routine plague diagnoses, especially in emergencies.
文摘Objective:To characterize the case fatality and estimate the symptomatic period of bubonic plague.Methods: Epidemiologic analyses of a previous outbreak of plague in Osaka and Kobe,two major port cities in Japan, from 1899-1900 were performed.In addition to date of onset of symptoms,gender,age and the date of death were extracted from the historical data.The time from onset to death(symptomatic period) was fitted to gamma distribution using the maximum likelihood method.Results:Temporal distribution revealed suspected chains of transmission of the primary pneumonic plague at the late stage of the outbreak.The case fatality of bubonic plague without specific treatment was 83.4%,and the mean time from onset to death was estimated as 4.7 days(95%confidence interval;4.0,5.5).Conclusion:Case fatality of bubonic plague without specific treatment was extremely high.The symptomatic period of bubonic plague appeared to be longer than that of pneumonic plague.
文摘More and more national investments go into the TCM industry in recent years,but few break-throughs have been made in the devel-opment of key theories or technologies.And the lack of innovation remains a problem and hinders the growth of the TCM industry.To solve the problem,the Twelfth Five-year Plan for
基金the National Natural Science Foundation of China(Grant Nos.30930001,30900823,and 30771179)the National Basic Research Program(973 Program)(Grant No.2009CB522600)。
文摘Flea-borne transmission is a recent evolutionary adaptation that distinguishes the deadly Yersinia pestis from its progenitor Y.pseudotuberculosis,a mild pathogen transmitted via the food-borne route.Y.pestis synthesizes biofilms in the flea gut,which is important for fleaborne transmission.Yersinia biofilms are bacterial colonies surrounded by extracellular matrix primarily containing a homopolymer of N-acetyl-D-glucosamine that are synthesized by a set of specific enzymes.Yersinia biofilm production is tightly regulated at both transcriptional and post-transcriptional levels.All the known structural genes responsible for biofilm production are harbored in both Y.pseudotuberculosis and Y.pestis,but Y.pestis has evolved changes in the regulation of biofilm development,thereby acquiring efficient arthropod-borne transmission.
文摘Plague,caused by Yersinia pestis,is a flea-borne disease that is endemic in areas throughout the world due to its successful maintenance in a sylvatic cycle,mainly in areas with temperate climates.Burrowing rodents are thought to play a key role in the enzootic maintenance as well as epizootic outbreaks of plague.In the United States,prairie dogs(Cynomys),rodents(Muridae),and ground squirrels(Spermophilus)are susceptible to infection and are parasitized by fleas that transmit plague.In particular,prairie dogs can experience outbreaks that rapidly spread,which can lead to extirpation of colonies.A number of ecological parameters,including climate,are associated with these epizootics.In this study,we asked whether soil parameters,primarily moisture and temperature,are associated with outbreaks of plague in black-tailed prairie dogs and Gunnison’s prairie dogs in the Western United States,and at what depth these associations were apparent.We collected publicly available county-level information on the occurrence of population declines or colony extirpation,while historical soil data was collected from SCAN and USCRN stations in counties and states where prairie dogs have been located.The analysis suggests that soil moisture at lower depths correlates with colony die-offs,in addition to temperature near the surface,with key differences within the landscape ecology that impact the occurrence of plague.Overall,the model suggests that the burrow environment may play a significant role in the epizootic spread of disease amongst black-tailed and Gunnison’s prairie dogs.
基金This work was funded by an internal research grant(Ref:PA 14.25)from the Institut Pasteur de MadagascarThis research was also funded in part by the Wellcome Trust[095171/Z/10/Z].
文摘The epidemiology of Yersinia pestis,the causative agent of plague,involves vectors and reservoirs in its transmission cycle.The passive plague surveillance in Madagascar targets mainly rodent and fleas.However,carnivores are routinely surveyed as sentinels of local plague activity in some countries.The aim of this study is to assess the use of domestic dog(Canis familiaris)as sentinel animal for field surveillance of plague in a highly endemic area in Madagascar.Cross-sectional surveys of plague antibody prevalence in C.familiaris were conducted in endemic areas with contrasting histories of plague cases in humans,as well as a plague free area.Rodent capture was done in parallel to evaluate evidence for Y.pestis circulation in the primary reservoirs.In 2 sites,dogs were later re-sampled to examine evidence of seroconversion and antibody persistence.Biological samplings were performed between March 2008 and February 2009.Plague antibody detection was assessed using anti-F1 ELISA.Our study showed a significant difference in dog prevalence rates between plague-endemic and plague-free areas,with no seropositive dogs detected in the plague free area.No correlation was found between rodents and dog prevalence rates,with an absence of seropositive rodents in some area where plague circulation was indicated by seropositive dogs.This is consistent with high mortality rates in rodents following infection.Re-sampling dogs identified individuals seropositive on both occasions,indicating high rates of re-exposure and/or persistence of plague antibodies for at least 9 months.Seroconversion or seropositive juvenile dogs indicated recent local plague circulation.In Madagascar,dog surveillance for plague antibody could be useful to identify plague circulation in new areas or quiescent areas within endemic zones.Within active endemic areas,monitoring of dog populations for seroconversion(negative to positive)or seropositive juvenile dogs could be useful for identifying areas at greatest risk of human outbreaks.
