The pyrin inflammasome and the Yersinia effector interaction

Pyrin is a cytosolic pattern-recognition receptor that normally functions as a guard to trigger capase-1 inflammasome assembly in response to bacterial toxins and effectors that inactivate RhoA. The MEFV gene encoding human pyrin is preferentially expressed in phagocytes. Key domains in pyrin include a pyrin domain (PYD), a linker region, and a B30.2 domain. Binding of ASC to pyrin by a PYD-PYD interaction triggers inflammasome assembly. Pyrin is held in an inactive conformation by negative regulation mechanisms to avoid premature inflammasome assembly. One mechanism of negative regulation involves phosphorylation of the linker by PRK kinase which in turn is positively regulated by active RhoA. The B30.2 domain also negatively regulates pyrin. Gain of function mutations in MEFV responsible for the autoinflammatory disease Familial Mediterranean Fever (FMF) map to exon 10 encoding the B30.2 domain. Insights into pyrin regulation have come from studies of several Yersinia effectors, which are injected into phagocytes and interact with the RhoA-PRK-pyrin axis during infection. Two effectors, YopE and YopT, inactivate RhoA to disrupt phagocytic signaling. To counteract an effector-triggered immune response, a third effector, YopM, binds to and inhibits pyrin by hijacking PRK and RSK and directing linker phosphorylation. Inhibition of pyrin by YopM is required for virulence of Yersinia pestis, the agent of plague. Recent results from infection studies with human phagocytes and mice producing pyrin B30.2 FMF variants show that gain of function MEFV mutations bypass inhibition by YopM. Population genetic data suggest that MEFV mutations were selected for in individuals of Mediterranean decent during historic plague pandemics. This review discusses current concepts of pyrin regulation and its interaction with Yersinia effectors.     

抗噬菌体鼠疫菌株的发现与研究

在天山山地灰旱獭鼠疫自然疫源地中,从病的灰旱獭体内分离出抗鼠疫噬菌体株。该菌株形态呈多形性,菌落不典型,对动物的毒力弱并失去抗源性;但经传代或冷冻干燥保存一段时间后,逐渐失去对鼠疫噬菌体的抗性,与此同时菌落形态转为R型,具有抗原性,对动物的毒力也随之增强。     

两种方法检测LGC盲样及效果探讨

目的：检测LGC盲样中的小肠结肠炎耶尔森氏菌并对过程和结果进行探讨。方法①分离培养法。②实时荧光PCR法。结果两者均检出小肠结肠炎耶尔森氏菌。结论两种方法的有效结合对目标菌检出有更重要的意义。     

中国鼠疫的疫情及防治进展

鼠疫是由鼠疫菌引起的烈性传染病,具有传染性强、传播速度快、病死率高的特点,严重危害人们的健康安全,甚至可能引发重大突发公共卫生事件。由于近年来我国仍有鼠疫病例报道,可见我国鼠疫防控形势仍然严峻,鼠疫的防治工作仍有待于加强。通过对1950—2019年全国鼠疫监测资料和21世纪以来报道的鼠疫病例的特征进行分析,进而了解我国鼠疫的疫情,探讨鼠疫的流行特点,提出相应的防控措施。新中国成立后,通过长期的防控,全国鼠疫疫情总体呈下降趋势,部分鼠疫自然疫源地已被消除;进入21世纪后鼠疫疫情呈现局灶性与散发性的特点,大多发生于西北地区和青藏地区,以青海省和西藏自治区较多,且主要与青壮年主动进入疫区或者接触鼠疫菌的宿主动物有关。应通过加大对疫区的监测,加强对人们的健康教育,正确诊断与高效治疗鼠疫患者,进而做好鼠疫的防治工作。     

Multiple Hepatic Abscesses Due to Yersinia enterocolitica Infection Secondary to Primary Haemochromatosis

A case of hepatic abscesses due to Yersinia enterocolitica in an immunocompetent male is presented. Reexamination after 3 months showed that the patient had primary haemochromatosis. Treatment with repeated phlebotomies was instituted. Two years after the patient was first admitted to hospital, 17.2 g iron had been removed and all haematological and biochemical parameters had returned to normal. Genetic analysis of the patients' two sons showed that one was positive for the chromosome defect found in primary haemochromatosis; further investigation is under progress. A study of the literature showed that prior to this case only 45 cases of hepatic abscess secondary to Yersinia enterocolitica have been registered. Of the 45 reported cases, 64% had underlying haemochromatosis and 29% had diabetes mellitus. The overall mortality was 31%. Mortality before 1987 was 60% (n = 20) and since 1987 it has been 8% (n = 25).     

Quinto Tiberio Angelerio and New Measures for Controlling Plague in 16th-Century Alghero,Sardinia

Plague, a zoonotic disease caused by the bacterium Yersinia pestis, has been responsible for at least 3 pandemics. During 1582–1583, a plague outbreak devastated the seaport of Alghero in Sardinia. By analyzing contemporary medical texts and local documentation, we uncovered the pivotal role played by the Protomedicus of Alghero, Quinto Tiberio Angelerio (1532–1617), in controlling the epidemic. Angelerio imposed rules and antiepidemic measures new to the 16th-century sanitary system of Sardinia. Those measures undoubtedly spared the surrounding districts from the spread of the contagion. Angelerio seems to have been an extremely successful public health officer in the history of plague epidemics in Sardinia.     

中国鼠疫自然疫源地分型研究Ⅳ.鼠疫耶尔森菌生物型生物学特征的探讨

鼠疫菌生物型是鼠疫菌起源进化遗传性状最稳定的生物学标准, 是鼠疫起源进化普系的“活化石”, 也是该菌起源进化最具代表性的模式.依据其对甘油和阿拉伯糖的酵解和还原硝酸盐的能力, 鼠疫菌可分为4种生物型, 即古典型(甘油酵解阳性, 阿拉伯糖酵解阳性, 硝酸盐还原阳性)、中世纪型(甘油酵解阳性, 阿拉伯糖酵解阳性, 硝酸盐还原阴性)、东方型(甘油酵解阴性, 阿拉伯糖酵解阳性, 硝酸盐还原阳性)和田鼠型(甘油酵解阳性, 阿拉伯糖酵解阴性, 硝酸盐还原阴性).前三种生物型与人类历史3次鼠疫大流行相对应, 最后一种生物型对人不致病, 但能造成田鼠鼠疫并在其自然疫源地内流行.目前中国鼠疫自然疫源地有4种鼠疫菌生物型.     

延吉机场口岸鼠类携带病原情况调查

目的 了解延吉机场口岸鼠类病原携带情况,为口岸传染病监测和媒介生物控制提供依据.方法 采用ELTON夹夜法捕鼠,搜集鼠类体表寄生虫、个体测量后解剖取鼠肺、肝、脾置于医用冻存管内,做好标记,保存于管液氮罐中,检测鼠疫菌、地方性斑疹伤寒立克次体、汉坦病毒.结果 本次调查共捕获鼠类150只,其中6份鼠肺汉坦病毒检测阳性.结论 应进一步开展口岸鼠类携带病原调查,掌握其变化规律.有针对性的开展预防与控制工作.     

鼠疫耶尔森菌TaqMan探针实时荧光定量PCR快速检测

目的 建立一种快速检测鼠疫耶尔森菌的方法.方法 以编码F1抗原的基因caf1为靶序列,人工合成基因序列,制备重组质粒作为鼠疫耶尔森菌检测的标准样品;用实时荧光定量聚合酶链反应(fluorescent quantitative polymerase chain reaction,FQ-PCR)技术,针对pMT1质粒上的caf1基因设计引物和TaqMan荧光探针,进行实时FQ-PCR检验,评价该方法的准确性、敏感性及特异性.建立鼠疫耶尔森菌TaqMan探针实时FQ-PCR检测方法.结果 本研究成功构建了质粒pUC57-caf1,引物、探针特异性良好,标准曲线在5.03×102～5.03×107拷贝数之间,具有较好的线性关系,相关系数1.0.实时FQ-PCR检验最低可检测出5.03×102拷贝数的重组质粒,灵敏度比普通PCR高100倍.特异性检测试验可选择性检测出鼠疫耶尔森菌,与其他细菌无交叉反应,结果与普通PCR一致.对同一浓度的重组质粒进行15个平行样品的重复性试验,Ct值标准差为0.28.结论 建立TaqMan探针实时FQ-PCR检测技术,能够快速、准确、特异的检测鼠疫耶尔森菌,为鼠疫监控、诊断提供技术支持.