pathogenicity

致病性
  • 文章类型: Journal Article
    人乳头瘤病毒(HPV)81型最近已成为最常见的低风险HPV类型之一;关注它的文献是有限的。本研究旨在分析HPV81检出率增高的原因,并探讨其致病力的演变过程。我们分析了从2014年到2023年收集的229061个脱落的宫颈细胞样本中HPV81的检出率和趋势;收集了来自两个不同时间段的HPV81单个感染的样本;并分析了等位基因频率,积极选择,病毒载量,持续性感染能力,E6和E7基因型的致病性。我们发现HPV81在宫颈脱落细胞中的检出率在低风险类型中排名第一,并表现出明显的上升趋势(p<0.001)。HPV81的E6原型等位基因的频率(n=317)显着增加(p=0.018),并表现出最强的适应能力。E6原型的病毒载量和持续感染能力明显高于突变体,从而成为提高HPV81检出率和增强其致病性的关键驱动因素。病毒载量与持续感染能力和致病性呈正相关。持续感染是HPV81致病性的关键因素。HPV81的成功适应性进化伴随着增强的致病性。
    Human papillomavirus (HPV) type 81 has recently become one of the most common low-risk HPV types; however, literature focusing on it is limited. This study aimed to analyze the reasons for the increased detection rate of HPV81 and investigate its evolving pathogenicity. We analyzed the detection rates and trends of HPV81 in 229 061 exfoliated cervical cell samples collected from 2014 to 2023; collected samples of HPV81 single infections from two different time periods; and analyzed the allele frequencies, positive selection, viral load, persistent infection capacity, and pathogenicity of E6 and E7 genotypes. We found that the detection rate of HPV81 ranked first among the low-risk types in exfoliated cervical cells and exhibited a significantly increasing trend (p < 0.001). The frequency of the E6 prototype allele of HPV81 (n = 317) was significantly increased (p = 0.018) and demonstrated the strongest adaptive capacity. The viral load and persistent infection capacity of the E6 prototype were significantly higher than those of the mutants, thus serving as key drivers for increasing the detection rate of HPV81 and enhancing its pathogenicity. The viral load was positively correlated with persistent infection capacity and pathogenicity. Persistent infection was a crucial factor in the pathogenicity of HPV81. Successful adaptive evolution of HPV81 is accompanied by enhanced pathogenicity.
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  • 文章类型: Journal Article
    嗜冷黄杆菌,细菌性冷水病的病原体,是毁灭性的,分布在世界各地,在内陆养鱼场造成重大经济损失的鱼类病原体。先前的流行病学研究表明,流行的克隆复合物(CC)在受疾病影响的鱼类物种中有所不同,例如虹鳟鱼,大麻哈鱼和ayu,表明特定的嗜冷F.基因型与宿主物种之间存在显着关联。然而,种群结构是由鱼类和卵的交易还是由宿主特异性致病性驱动的,目前尚不确定。值得注意的是,从ayu中检索到的所有嗜冷菌分离株都属于3型O抗原(O-Ag),而从其他鱼类中检索到的菌株中只有极少数具有这种O-Ag,表明在影响ayu的疫情中的作用。因此,我们调查了基因型和致病性之间的联系,通过进行比较浴感染挑战在两个鱼宿主,ayu和虹鳟鱼,代表不同MLST基因型和O-Ag的分离株的集合。一种宿主物种中的高毒力菌株在另一种宿主物种中表现出低至无毒力。F.与ayu相关并具有3型O-Ag的嗜冷菌菌株在ayu的致病性方面表现出明显的变异性,从无毒到高毒性。引人注目的是,F.从虹鳟鱼中回收并具有3型O-Ag的嗜冷菌菌株对虹鳟鱼具有毒力,但对ayu没有毒力,表明单独的3型O-Ag不足以在ayu中产生致病性,它也不会阻止虹鳟鱼的致病性。这项研究表明,特定CC与宿主物种之间的关联部分取决于病原体对特定宿主物种的适应。
    Flavobacterium psychrophilum, the causative agent of bacterial cold-water disease, is a devastating, worldwide distributed, fish pathogen causing significant economic loss in inland fish farms. Previous epidemiological studies showed that prevalent clonal complexes (CC) differ in fish species affected with disease such as rainbow trout, coho salmon and ayu, indicating significant associations between particular F. psychrophilum genotypes and host species. Yet, whether the population structure is driven by the trade of fish and eggs or by host-specific pathogenicity is uncertain. Notably, all F. psychrophilum isolates retrieved from ayu belong to Type-3 O antigen (O-Ag) whereas only very few strains retrieved from other fish species possess this O-Ag, suggesting a role in outbreaks affecting ayu. Thus, we investigated the links between genotype and pathogenicity by conducting comparative bath infection challenges in two fish hosts, ayu and rainbow trout, for a collection of isolates representing different MLST genotypes and O-Ag. Highly virulent strains in one host species exhibited low to no virulence in the other. F. psychrophilum strains associated with ayu and possessing Type-3 O-Ag demonstrated significant variability in pathogenicity in ayu, ranging from avirulent to highly virulent. Strikingly, F. psychrophilum strains retrieved from rainbow trout and possessing the Type-3 O-Ag were virulent for rainbow trout but not for ayu, indicating that Type-3 O-Ag alone is not sufficient for pathogenicity in ayu, nor does it prevent pathogenicity in rainbow trout. This study revealed that the association between a particular CC and host species partly depends on the pathogen\'s adaptation to specific host species.
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  • 文章类型: Journal Article
    背景:长期以来,人们一直认为ABO血型是影响感染性疾病易感性的重要因素。许多研究探索了ABO血型与感染COVID-19的可能性和感染的严重程度之间的联系,产生相互矛盾的结果。
    目的:本研究旨在确定年龄的影响,性别,ABO血型,和Rh因子对COVID-19感染潜在发展的影响。
    方法:横截面,观察性研究收集的数据包括年龄,性别,ABO血型,和来自乌代浦尔R.R.牙科学院和医院的80名医疗保健专业人员的Rh因子,这些专业人员通过谷歌表格(谷歌有限责任公司,山景,加州,美国)。卡方统计评估了样本中血型和抗体的分布。使用Windows版IBM社会科学统计软件包(SPSS)的21.0版(IBMCorp,Armonk,NY).
    结果:在这项研究中,O型血占45.2%(n=33),A型为21.9%(n=16),B型为24.7%(n=18),AB型为8.2%(n=6)。Rh阳性样本为87.7%(n=64),Rh阴性样本为12.3%(n=9)。A型(p=0.001)和O型(p=0.049)之间存在统计学上的显着相关性。31名参与者(42.5%)年龄在20-30岁之间,26人(35.6%)年龄在31-40岁之间,16人(21.9%)年龄在41-50岁之间。统计学分析显示各年龄组间差异无统计学意义(p>0.05)。
    结论:患者的性别,年龄,和并发疾病是决定严重急性呼吸道综合征-冠状病毒2(SARS-CoV-2)感染严重程度的关键风险变量.越来越多的数据表明,ABO血型在生理和生化水平的疾病生物学中具有重要作用。因此,这项研究增加了有价值的信息,以加强和建立因素的潜在作用,比如年龄和性别,在COVID-19感染的可能致病性中。
    BACKGROUND: The ABO blood group has long been recognized as a significant factor influencing susceptibility to infectious diseases. Numerous studies have explored the links between ABO blood types and both the likelihood of contracting COVID-19 and the severity of the infection, yielding conflicting results.
    OBJECTIVE: This study intends to determine the influence of age, gender, the ABO blood group, and Rh factor on the potential development of COVID-19 infection.
    METHODS: A cross-sectional, observational study collected data including age, gender, the ABO blood group, and Rh factor from 80 healthcare professionals at R. R. Dental College and Hospital in Udaipur with a positive history of COVID-19 infection via Google Forms (Google LLC, Mountain View, California, United States). Chi-square statistics assessed the distribution of blood types and antibodies within the samples. Odds ratio (OR) assays were used to assess the probability of a certain blood type or Rh factor with version 21.0 of the IBM Statistical Package for Social Sciences (SPSS) for Windows (IBM Corp, Armonk, NY).
    RESULTS: In this study, the blood group type O was 45.2% (n = 33), type A was 21.9% (n = 16), type B was 24.7% (n = 18), and type AB was 8.2% (n = 6). Rh-positive samples were 87.7% (n = 64) and Rh-negative samples were 12.3% (n = 9). There was a statistically significant correlation between Type A (p = 0.001) and Type O (p = 0.049). Thirty-one participants (42.5%) were aged 20-30 years, 26 (35.6%) were aged 31-40 years, and 16 (21.9%) were aged 41-50 years. The statistical analysis revealed no statistically significant distinction among the age groups (p > 0.05).
    CONCLUSIONS: The patients\' gender, age, and concurrent disorders are crucial risk variables that determine the severity of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. There is growing data indicating that the ABO blood group has a significant role in disease biology at physiological and biochemical levels. Hence, this study adds valuable information to strengthen and establish the potential role of factors, such as age and gender, in the possible pathogenicity of COVID-19 infection.
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  • 文章类型: Journal Article
    这篇全面的综述探讨了产志贺毒素大肠杆菌(STEC)的致病性和检测,阐明其各种遗传和临床表现。源自大肠杆菌的STEC通过移动性和遗传元件获得致病性。从临床进展的角度探讨了STEC的致病性,并发症,和关键毒素,如志贺毒素(Stx)。Stx1和Stx2是两种不同的Stx类型,表现出不同的毒性,与Stx2经常与严重的疾病相关。这篇综述还深入研究了枯草杆菌酶细胞毒素,由一些STEC菌株产生的额外的细胞毒素。STEC的致病机制,如附着和去除肠道病变,讨论,关注遗传因素的作用。STEC中的质粒可以赋予独特的致病性。与其他致病性大肠杆菌杂交可以产生更致命的病原体。这篇综述涵盖了一系列的检测方法,从DNA扩增到抗原检测技术,强调需要创新方法来提高STEC诊断的灵敏度和速度。总之,了解STEC致病性的各个方面并探索增强的诊断方法对于有效解决这种食源性病原体至关重要。志贺毒素毒性的病理学。STEC衍生的志贺毒素由一个A亚基和五个B亚基组成。该疾病的病理症状可在腹泻发作后两周内发展为HUS。志贺毒素中毒也与许多并发症有关,如神经和心脏并发症。该图是根据Bruyand等人的数据重建的。
    This comprehensive review delves into the pathogenicity and detection of Shiga Toxin-Producing Escherichia coli (STEC), shedding light on its various genetic and clinical manifestations. STEC originating from E. coli acquires pathogenicity through mobility and genetic elements. The pathogenicity of STEC is explored in terms of clinical progression, complications, and key toxins such as Shiga toxin (Stx). Stx1 and Stx2 are two distinct Stx types exhibiting different toxicities, with Stx2 often associated with severe diseases. This review also delves into Subtilase cytotoxin, an additional cytotoxin produced by some STEC strains. Pathogenic mechanisms of STEC, such as attaching and effacing intestinal lesions, are discussed, with a focus on roles of genetic factors. Plasmids in STEC can confer unique pathogenicity. Hybridization with other pathogenic E. coli can create more lethal pathogens. This review covers a range of detection methods, ranging from DNA amplification to antigen detection techniques, emphasizing the need for innovative approaches to improve the sensitivity and speed of STEC diagnosis. In conclusion, understanding diverse aspects of STEC pathogenicity and exploring enhanced diagnostic methods are critical to addressing this foodborne pathogen effectively. Pathology of Shiga toxin toxicity. STEC-derived Shiga toxin consists of one A subunit and five B subunits. Pathological symptoms of the disease can progress to HUS within two weeks after the onset of diarrhea. Shiga toxin intoxication is also associated with many complications, such as neurological and cardiac complications. This figure was reconstructed based on data from Bruyand et al.
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  • 文章类型: Journal Article
    烟杆菌属。是在各种作物中引起软腐病症状的重要细菌病原体。然而,他们的致病机制需要明确,以帮助控制他们的感染。这里,全基因组关联研究(GWAS)是通过整合基因组数据和两种表型(毒力和纤维素酶活性)的测量来进行的,以确定其致病性的遗传基础。开发了基于人工智能的软件程序来自动测量大白菜上的病变面积,从而促进准确和快速的数据收集毒力表型用于GWAS分析。分析发现428个和158个基因座与弯曲杆菌毒力(病变面积)和纤维素酶活性显着相关,分别。此外,鉴定了1,229个和586个上位位点对的毒力和纤维素酶活性表型,分别。其中,AraC转录调节因子与另外三个与营养转运相关的基因成对产生毒力表型,实验证实了它们的上位效应,其中一对具有每个单基因和双基因的敲除突变体。因此,这项研究为感染杆菌属的遗传机制提供了有价值的见解。致病性。重要性植物病虫害是造成多达40%粮食作物损失的原因,每年因植物病害造成的经济损失达2200多亿美元。与植物病害作斗争需要了解病原体的致病机制。本研究采用了一种先进的方法,将群体基因组学与毒力相关的表型数据结合在一起,以研究鸡杆菌属的遗传基础。,这在全球范围内造成了严重的作物损失。开发了基于人工智能的自动化软件程序来测量毒力表型(病变面积),这极大地促进了这项研究。该分析预测了与毒力表型高度相关的关键基因组基因座,表现出上位效应,并进一步证实突变基因缺失实验对毒力至关重要。本研究提供了与淋球菌致病性相关的遗传决定因素的新见解,并提供了一种有价值的新软件资源,可用于改善植物感染测量。
    Pectobacterium spp. are important bacterial pathogens that cause soft rot symptoms in various crops. However, their mechanism of pathogenicity requires clarity to help control their infections. Here, genome-wide association studies (GWAS) were conducted by integrating genomic data and measurements of two phenotypes (virulence and cellulase activity) for 120 various Pectobacterium strains in order to identify the genetic basis of their pathogenicity. An artificial intelligence-based software program was developed to automatically measure lesion areas on Chinese cabbage, thereby facilitating accurate and rapid data collection for virulence phenotypes for use in GWAS analysis. The analysis discovered 428 and 158 loci significantly associated with Pectobacterium virulence (lesion area) and cellulase activity, respectively. In addition, 1,229 and 586 epistasis loci pairs were identified for the virulence and cellulase activity phenotypes, respectively. Among them, the AraC transcriptional regulator exerted epistasis effects with another three nutrient transport-related genes in pairs contributing to the virulence phenotype, and their epistatic effects were experimentally confirmed for one pair with knockout mutants of each single gene and double gene. This study consequently provides valuable insights into the genetic mechanism underlying Pectobacterium spp. pathogenicity. IMPORTANCE Plant diseases and pests are responsible for the loss of up to 40% of food crops, and annual economic losses caused by plant diseases reach more than $220 billion. Fighting against plant diseases requires an understanding of the pathogenic mechanisms of pathogens. This study adopted an advanced approach using population genomics integrated with virulence-related phenotype data to investigate the genetic basis of Pectobacterium spp., which causes serious crop losses worldwide. An automated software program based on artificial intelligence was developed to measure the virulence phenotype (lesion area), which greatly facilitated this research. The analysis predicted key genomic loci that were highly associated with virulence phenotypes, exhibited epistasis effects, and were further confirmed as critical for virulence with mutant gene deletion experiments. The present study provides new insights into the genetic determinants associated with Pectobacterium pathogenicity and provides a valuable new software resource that can be adapted to improve plant infection measurements.
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  • 文章类型: Journal Article
    副溶血性弧菌可引起人海产品传播的胃肠炎感染,甚至可导致死亡。副溶血弧菌的致病菌株分泌不同类型的毒力因子,这些毒力因子通过不同类型的分泌系统直接注射到宿主细胞中,这有助于细菌在生物体内建立自己的生态位。因此,这项研究的目的是从副溶血性弧菌的trh阳性菌株中分离细胞外分泌蛋白,并使用二维凝胶电泳和MALDI-TOFMS/MS进行鉴定。17种不同的细胞蛋白质,氨基甲酰磷酸合成酶,5-甲基四氢蝶酰三谷氨酸,tRNA-二氢尿苷合成酶,甘油-3-磷酸脱氢酶,泊苷5'-磷酸脱羧酶,钼进口ATP结合蛋白,DnaJ,DNA聚合酶IV,核糖体RNA小亚基甲基转移酶G,ATP合酶亚基δ和γ,核糖体回收因子,4-羟基-3-甲基丁-2-烯-1-基二磷酸合酶,tRNA假尿苷合成酶B,迪特兰,聚顺式-十一烯基二磷酸合成酶,氧依赖性的卟啉原-III氧化酶,和肽脱甲酰基酶2被鉴定为主要参与不同的代谢和生物合成途径。此外,鉴定的蛋白质的分子功能与催化活性有关,连接酶活性,运输机,金属装订,和ATP合成酶,当他们在细胞间。然而,为了了解这些分泌蛋白在宿主细胞内细菌感染和存活中的重要性,进行了病原体-宿主蛋白-蛋白相互作用(PPI),该相互作用鉴定了8种分泌蛋白与参与不同细胞途径的41种人类蛋白的关联。包括泛素化降解,附着力,炎症,豁免权,和程序性细胞死亡。本研究为成功建立感染和细胞内繁殖提供了有关宿主细胞环境生存和适应机制的未报道策略。
    Vibrio parahaemolyticus causes seafood-borne gastroenteritis infection in human which can even lead to death. The pathogenic strain of V. parahaemolyticus secretes different types of virulence factors that are directly injected into the host cell by a different type of secretion system which helps bacteria to establish its own ecological niche within the organism. Therefore, the aim of this study was to isolate the extracellular secreted proteins from the trh positive strain of V. parahaemolyticus and identify them using two-dimensional gel electrophoresis and MALDI-TOFMS/MS. Seventeen different cellular proteins viz, Carbamoyl-phosphate synthase, 5-methyltetrahydropteroyltriglutamate, tRNA-dihydrouridine synthase, Glycerol-3-phosphate dehydrogenase, Orotidine 5\'-phosphate decarboxylase, Molybdenum import ATP-binding protein, DnaJ, DNA polymerase IV, Ribosomal RNA small subunit methyltransferase G, ATP synthase subunit delta and gamma, Ribosome-recycling factor, 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, tRNA pseudouridine synthase B, Ditrans, polycis-undecaprenyl-diphosphate synthase, Oxygen-dependent coproporphyrinogen-III oxidase, and Peptide deformylase 2 were identified which are mainly involved in different metabolic and biosynthetic pathways. Furthermore, the molecular function of the identified proteins were associated with catalytic activity, ligase activity, transporter, metal binding, and ATP synthase when they are intercellular. However, to understand the importance of these secreted proteins in the infection and survival of bacteria inside the host cell, pathogen-host protein-protein interactions (PPIs) were carried out which identified the association of eight secreted proteins with 41 human proteins involved in different cellular pathways, including ubiquitination degradation, adhesion, inflammation, immunity, and programmed cell death. The present study provides unreported strategies on host-cell environment\'s survival and adaptation mechanisms for the successful establishment of infections and intracellular propagation.
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  • 文章类型: Journal Article
    在2010-2011年冬季,日本在野生鸟类中爆发了由进化枝2.3.2.1H5N1高致病性禽流感病毒(HPAIV)引起的大规模感染。有趣的是,许多簇绒鸭(Aythyafuligula),它们是迁徙潜水鸭,死于感染,而迁徙涉猎鸭只报告了一例感染病例,甲型流感病毒的主要自然宿主,在爆发期间。为了评估每种鸭种对HPAIV的易感性是否与病例数相关,簇绒鸭和涉猎鸭物种(欧亚wigeon,马里卡·佩内洛普;野鸭,Anasplatyrhynchos;北方平尾,Anasacuta)鼻内接种A/普通话/宫崎/22M807-1/2011(H5N1),一种索引进化枝2.3.2.1病毒,以前用于各种鸟类的实验性感染研究。接种后(dpi)10天观察到的所有鸭子大多通过口服途径脱离病毒并存活。簇绒鸭的病毒滴度比其他涉猎鸭更高,其中一个在7dpi后表现出明显的神经症状,伴有眼部病变。在涉猎的鸭子中没有观察到临床症状,尽管在3dpi时处死的一些患者中观察到全身性感染和病毒血症。这些结果表明,进化枝2.3.2.1HPAIV的易感性可能因鸭种而异。
    In the winter of 2010-2011, Japan experienced a large outbreak of infections caused by clade 2.3.2.1 H5N1 high pathogenicity avian influenza viruses (HPAIVs) in wild birds. Interestingly, many tufted ducks (Aythya fuligula), which are migratory diving ducks, succumbed to the infection, whereas only one infection case was reported in migratory dabbling duck species, the major natural hosts of the influenza A virus, during the outbreak. To assess whether the susceptibility of each duck species to HPAIVs was correlated with the number of cases, tufted duck and dabbling duck species (Eurasian wigeon, Mareca penelope; mallard, Anas platyrhynchos; Northern pintail, Anas acuta) were intranasally inoculated with A/Mandarin duck/Miyazaki/22M807-1/2011 (H5N1), an index clade 2.3.2.1 virus previously used for experimental infection studies in various bird species. All ducks observed for 10 days post-inoculation (dpi) mostly shed the virus via the oral route and survived. The tufted ducks shed a higher titer of the virus than the other dabbling duck species, and one of them showed apparent neurological symptoms after 7 dpi, which were accompanied by eye lesions. No clinical symptoms were observed in the dabbling ducks, although systemic infection and viremia were observed in some of them sacrificed at 3 dpi. These results suggest that the susceptibility of clade 2.3.2.1 HPAIVs might differ by duck species.
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  • 文章类型: Journal Article
    尽管肺炎球菌疫苗的广泛实施,高毒力肺炎链球菌血清型19A在世界范围内流行。尚不清楚特定的遗传元件是否有助于血清型19A分离株的复杂致病性。我们对1,292个血清型19A分离株进行了大规模的全基因组关联研究(pan-GWAS),这些分离株来自侵袭性疾病和无症状携带者。为了解决潜在的疾病相关基因型,使用三种方法(Scorary,线性混合模型,和随机森林)进行比较疾病和运输分离株,以鉴定与疾病表型一致相关的基因。通过使用三种pan-GWAS方法,我们在基因型和疾病表型(疾病或携带)之间的统计学显著关联方面达成共识,具有30个一致重要的疾病相关基因的子集。功能注释的结果表明,这些疾病相关基因具有不同的预测功能,包括那些参与移动遗传元件的,抗生素耐药性,毒力,和细胞代谢。我们的发现表明这种高毒力血清型具有多因素致病性,并为设计新型基于蛋白质的疫苗以预防和控制肺炎球菌疾病提供了重要证据。重要性了解肺炎链球菌血清型19A的遗传和致病特征非常重要,这可能为肺炎球菌疾病的预防和治疗提供重要信息。这项全球大样本泛GWAS研究已经确定了30个始终重要的疾病相关基因的子集,这些基因与移动遗传元件有关。抗生素耐药性,毒力,和细胞代谢。这些发现表明了高毒力肺炎链球菌血清型19A分离株的多因素致病性性质,并为新型基于蛋白质的疫苗的设计提供了启示。
    Despite the widespread implementation of pneumococcal vaccines, hypervirulent Streptococcus pneumoniae serotype 19A is endemic worldwide. It is still unclear whether specific genetic elements contribute to complex pathogenicity of serotype 19A isolates. We performed a large-scale pan-genome-wide association study (pan-GWAS) of 1,292 serotype 19A isolates sampled from patients with invasive disease and asymptomatic carriers. To address the underlying disease-associated genotypes, a comprehensive analysis using three methods (Scoary, a linear mixed model, and random forest) was performed to compare disease and carriage isolates to identify genes consistently associated with disease phenotype. By using three pan-GWAS methods, we found consensus on statistically significant associations between genotypes and disease phenotypes (disease or carriage), with a subset of 30 consistently significant disease-associated genes. The results of functional annotation revealed that these disease-associated genes had diverse predicted functions, including those that participated in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. Our findings suggest the multifactorial pathogenicity nature of this hypervirulent serotype and provide important evidence for the design of novel protein-based vaccines to prevent and control pneumococcal disease. IMPORTANCE It is important to understand the genetic and pathogenic characteristics of S. pneumoniae serotype 19A, which may provide important information for the prevention and treatment of pneumococcal disease. This global large-sample pan-GWAS study has identified a subset of 30 consistently significant disease-associated genes that are involved in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. These findings suggest the multifactorial pathogenicity nature of hypervirulent S. pneumoniae serotype 19A isolates and provide implications for the design of novel protein-based vaccines.
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  • 文章类型: Journal Article
    鸡传染性贫血(CIA)是由鸡贫血病毒(CAV)引起的。最近,中国家禽养殖场的蛋鸡(8至10周龄)出现了严重的贫血。然而,在6周龄或以上的鸡中,CAV的病因特征和致病潜力尚不清楚。在这项研究中,我们分离出一个CAV菌株,SD15,来自两个月大的严重贫血鸡,并分析了遗传进化关系。我们发现菌株SD15与CAV18菌株具有最高的同源性(98.9%)。与33个参考菌株的比较揭示了菌株SD15中的16个氨基酸突变,其中两个是先前未知的(VP1中的F210S和Vp3中的L25S)。与低致病性菌株(Cux-1和C14)相比,高致病性菌株(SDLY08和SD15)在其非编码区存在3个碱基突变。为了进一步了解其致病性,用新型菌株和SDLY08攻击10周龄的无特定病原体(SPF)鸡。SDLY08组未见明显临床症状。然而,感染SD15的鸡表现出明显的生长迟缓和免疫抑制。免疫抑制的主要表现为胸腺和法氏囊指数显著降低以及AIV-H9疫苗诱导的抗体水平(P<0.05)。SD15组的红细胞数量最低,仅为对照组的60%。一起来看,新型菌株SD15不仅表现出更高的致病性,而且还表现出打破老年鸡对CAV的年龄抗性的潜在能力。我们的研究增强了对感染严重贫血的鸡的流行病学特征的了解,并有助于在中国制定改进的CIA控制策略。
    Chicken infectious anemia (CIA) is caused by chicken anemia virus (CAV). Recently, severe anemia has emerged in layer chickens (8 to 10-week-old) on poultry farms in China. However, the etiological characteristics and pathogenic potential of CAV in chickens at 6 weeks or older are not well understood. In this study, we isolated a CAV strain, termed SD15, from two-month-old chicken with severe anemia and analyzed the genetic evolution relationship. We found that strain SD15 had the highest homology (98.9%) with CAV18 strain. Comparison with 33 reference strains revealed 16 amino acid mutations in strain SD15, two of which were previously unknown (F210S in VP1 and L25S in Vp3). Compared with low pathogenic strains (Cux-1 and C14), highly pathogenic strains (SDLY08 and SD15) had three base mutations in their noncoding region. To further understand its pathogenicity, 10-week-old specific-pathogen-free (SPF) chickens were challenged with the novel strain and SDLY08. No obvious clinical symptoms were observed in the SDLY08 group. However, SD15-infected chickens showed significant growth retardation and immunosuppression. The main manifestations of immunosuppression were the significantly reduced thymus and bursa indices and AIV-H9 vaccine-induced antibody levels (P < 0.05). The lowest number of red blood cells in the SD15 group was just 60% of that in the control group. Taken together, the novel strain SD15 not only showed higher pathogenicity but also exhibited the potential ability to break the age resistance of older chickens to CAV. Our study enhanced the understanding of the epidemiological characteristics of chickens infected with severe anemia and can facilitate the development of improved control strategies of CIA in China.
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  • 文章类型: Journal Article
    产生志贺毒素的大肠杆菌(STEC)感染可引起从腹泻到潜在致命的溶血性尿毒综合征(HUS)的临床表现。这项研究旨在确定与瑞典HUS发展相关的STEC遗传因素。这项研究共纳入了1994年至2018年间瑞典有和没有HUS的STEC感染患者的238个STEC基因组。血清型,志贺毒素基因(stx)亚型,和毒力基因的特征是与临床症状(HUS和非HUS)相关,并进行了全基因组关联研究。65株属于O157:H7,173株属于非O157血清型。我们的研究表明,在瑞典的HUS患者中最常见于O157:H7血清型菌株,尤其是进化枝8。stx2a和stx2a+stx2c亚型与HUS显著相关。与HUS相关的其他毒力因子主要包括内膜蛋白(eae)及其受体(tir),粘附因子,毒素,和分泌系统蛋白。Pangenome广泛关联研究确定了HUS-STEC菌株中辅助基因的数量显着过剩,包括编码外膜蛋白的基因,转录调节因子,噬菌体相关蛋白质,和许多与假设蛋白质相关的基因。全基因组系统发育和全基因组多重对应分析不能区分HUS-STEC和非HUS-STEC菌株。在O157:H7集群中,来自HUS患者的菌株紧密聚集;然而,在患有和不患有HUS的患者的O157菌株中,毒力基因均未发现显着差异。这些结果表明,来自不同系统发育背景的STEC菌株可能独立获得决定其致病性的基因,并证实其他非细菌因素和/或细菌-宿主相互作用可能影响STEC发病机理。
    Shiga toxin-producing Escherichia coli (STEC) infection can cause clinical manifestations ranging from diarrhea to potentially fatal hemolytic uremic syndrome (HUS). This study is aimed at identifying STEC genetic factors associated with the development of HUS in Sweden. A total of 238 STEC genomes from STEC-infected patients with and without HUS between 1994 and 2018 in Sweden were included in this study. Serotypes, Shiga toxin gene (stx) subtypes, and virulence genes were characterized in correlation to clinical symptoms (HUS and non-HUS), and pan-genome wide association study was performed. Sixty-five strains belonged to O157:H7, and 173 belonged to non-O157 serotypes. Our study revealed that strains of O157:H7 serotype especially clade 8 were most commonly found in patients with HUS in Sweden. stx2a and stx2a + stx2c subtypes were significantly associated with HUS. Other virulence factors associated with HUS mainly included intimin (eae) and its receptor (tir), adhesion factors, toxins, and secretion system proteins. Pangenome wide-association study identified numbers of accessory genes significantly overrepresented in HUS-STEC strains, including genes encoding outer membrane proteins, transcriptional regulators, phage-related proteins, and numerous genes related to hypothetical proteins. Whole-genome phylogeny and multiple correspondence analysis of pangenomes could not differentiate HUS-STEC from non-HUS-STEC strains. In O157:H7 cluster, strains from HUS patients clustered closely; however, no significant difference in virulence genes was found in O157 strains from patients with and without HUS. These results suggest that STEC strains from different phylogenetic backgrounds may independently acquire genes determining their pathogenicity and confirm that other non-bacterial factors and/or bacteria-host interaction may affect STEC pathogenesis.
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