SARS coronavirus induces apoptosis in Vero E6 cells

Severe acute respiratory syndrome (SARS) is an emerging infectious disease. Its etiological agent has been convincingly identified as a new member of family Coronaviridae (SARS-CoV). It causes serious damage to the respiratory system yet the mechanism is not clear. Infection-induced apoptosis or necrosis is suspected but no direct evidence for this yet exists. To date, Vero E6 cells are the only cell line that could be used to replicate the virus with obvious CPE (cytopathic effect) in vitro. It is known for some viruses (including members of family Coronaviridae) that CPE can be caused either by virus-induced apoptosis (active death) or cell necrosis (passive death). In this study, we examined the apoptosis in the SARS-CoV infected Vero E6 cells. Indeed, the results do show that the CPE was induced by apoptosis rather than necrosis, shown by typical DNA fragmentation, through the existence of apoptotic bodies and swollen mitochondria. This observation has some implications for the SARS-CoV pathogenicity: SARS-CoV does induce apoptosis in cell cultures and might have the same effect in vivo, responsible for the severe damage of the respiratory system.     

Exomic variants of an elderly cohort of Brazilians in the ABraOM database

Brazilians are highly admixed with ancestry from Europe, Africa, America, and Asia and yet still underrepresented in genomic databanks. We hereby present a collection of exomic variants from 609 elderly Brazilians in a census‐based cohort (SABE609) with comprehensive phenotyping. Variants were deposited in ABraOM (Online Archive of Brazilian Mutations), a Web‐based public database. Population representative phenotype and genotype repositories are essential for variant interpretation through allele frequency filtering; since elderly individuals are less likely to harbor pathogenic mutations for early‐ and adult‐onset diseases, such variant databases are of great interest. Among the over 2.3 million variants from the present cohort, 1,282,008 were high‐confidence calls. Importantly, 207,621 variants were absent from major public databases. We found 9,791 potential loss‐of‐function variants with about 300 mutations per individual. Pathogenic variants on clinically relevant genes (ACMG) were observed in 1.15% of the individuals and were correlated with clinical phenotype. We conducted incidence estimation for prevalent recessive disorders based upon heterozygous frequency and concluded that it relies on appropriate pathogenicity assertion. These observations illustrate the relevance of collecting demographic data from diverse, poorly characterized populations. Census‐based datasets of aged individuals with comprehensive phenotyping are an invaluable resource toward the improved understanding of variant pathogenicity.     

Identification of in-vivo induced genes of Streptococcus suis serotype 2 specially expressed in infected human

Streptococcus suis (S. suis) serotype 2 usually cause infection in swine. Recently, two large-scale outbreaks in China with severe streptococcal toxic shock syndrome (STSS) and high mortality raised worldwide concern to human S. suis infection. To reveal the molecular pathogenesis of S. suis 2 during human infection, in-vivo induced antigen technology (IVIAT) was applied to identify the in-vivo induced genes (ivi genes) of S. suis 05ZYH33. The ivi genes are specifically expressed or up-regulated in-vivo and always associated with the in-vivo survival and pathogenicity of pathogens. In present study, convalescent sera from S. suis 05ZYH33 infected patients were pooled and fully adsorbed with in-vitro grown S. suis 05ZYH33 and Escherichia coli BL21 (DE3). Genomic expression library of 05ZYH33 was repeatedly screened with colony immunoblot assay using adsorbed sera. Finally, 19 genes were assessed as ivi genes of 05ZYH33. Fifteen of 19 genes encode proteins with biological functions in substance transport and metabolism, cell structure biogenesis, cell cycle control, replication, translation and other functions. The 4 remaining genes encode proteins with unknown functions. Of the 19 ivi genes, five (SSU05_0247, 0437, 1577, 1664 and 2144) encode proteins with no immunoreactivity to control sera from healthy individuals never exposed to 05ZYH33. The successful identification of ivi genes not only sheds light on understanding the pathogenesis of S. suis 05ZYH33 during its human infection, but also provides potential targets for the developments of new vaccines, therapeutic drugs and diagnostic reagents against human S. suis infection.     

neuB1失活空肠弯曲菌O∶19突变株感染致病力的初步研究

目的探讨neuB1失活空肠弯曲菌(Campylobacter jejuni,CJ)O∶19突变株的感染致病力。方法由CJ O∶19野生株构建neuB1灭活的突变株,检测其对正常人血清杀菌活性的敏感性、运动力和自身凝集(AAG)活性,并与野生株进行比较。结果突变株对10%正常成人血清(normal human serum,NHS)杀菌活性的敏感性高于同源的野生株(P<0.05),孵育15min和60min后突变株存活率分别为(20.6±7.4)%和(9.6±3.6)%,而野生株分别为(36.9±5.9)%和(15.5±4.3)%,但突变株的运动力和AAG活性与野生株比较却没有显著性差异(P>0.05)。结论neuB1失活CJ O∶19突变株仍具有较强的感染致病力,因而应考虑灭活后突变菌株疫苗的开发研究。     

Studies on hyaluronidase, chondroitin sulphatase, proteinase and phospholipase secreted by Candida species

Summary. We studied the ability of different Candida species to produce, at the same time, hyaluronidase, chondroitin sulphatase, proteinase, and phospholipase to assess whether they could be related to Candida pathogenicity. Only C. albicans was able to produce the four enzymes tested (73%) and was highly virulent to mice. Strains, that lack the capacity to produce one or more of the enzymes assayed, seemed less virulent or avirulent, similarly to the spontaneous hyaluronidase, chondroitin sulphatase, phospholipase and proteinase-deficient C. albicans strain FCF 14,1 which was non-pathogenic to mice. Among the other Candida species tested, none of them produced the four enzymes simultaneously, being less virulent in intravenously inoculated mice.
Zusammenfassung. Es wurde die Fähigkeit mehrerer Candida -Arten, gleichzeitig Hyaluronidase-, Chondroitinsulfatase-, Proteinase- und Phospholipase-Aktivität auszubilden, untersucht und deren Bedeutung als Candida -Pathogenitäts-merkmal bewertet. Nur C. albicans -Stämme waren in der Lage, die vier Enzyme zu bilden und waren für Mäuse hochvirulent. Stämme, welchen die Fähigkeit fehlte, eines oder mehrere dieser Enzyme zu produzieren, schienen weniger virulent oder avirulent zu sein, ähnlich wie der C. albicans -Stamm FCF 14,1, der spontan defizient für alle vier Enzyme war und der sich als nichtpathogen für Mäuse erwies. Von allen übrigen getesteten Candida -Arten produzierte keine gleichzeitig alle vier Enzyme, und diese erwiesen sich bei intravenöser Infektion als weniger virulent für Mäuse.     

解脲脲原体感染与女性生殖系统疾病的关系

解脲脲原体（Ureaplasma urealyticum，UU）是女性泌尿生殖系统感染的常见病原体之一，且近年来其感染呈增多趋势。本文就UU的致病物质、相关动物模型的建立、UU与各种女性生殖系统疾病的相关性研究等方面进行综述。旨在对女性感染UU实现早检查、早诊断、早治疗，以利改善预后。     

A genomic population genetics analysis of the pathogenic enterocyte effacement island in Escherichia coli: the search for the unit of selection

Comparative genomic analysis is a powerful tool for understanding the history and organization of complete genomes. The mathematical tools of population genetics combined with genomic analysis provide a powerful approach to dissect heterogeneities in genome evolution. This study presents a hierarchical analysis of the enterocyte and effacement island (35 kb), which is found in the enteropathogenic and enterohemorrhagic strains in Escherichia coli and in Citrobacter rodentium. The locus of enterocyte and effacement in E. coli is considered to be a clonal unit inside a clonal organism and is expected to evolve as a single unit. This analysis examines the clonal assumption by determining genetic diversity, GC content, and the substitution rates at the different functional levels of (i) the complete pathogenic island, (ii) the five operons in which the island is organized, and (iii) for each of the individual 41 genes that comprise the locus. We find that there is a conserved region that is composed of genes that belong to the type III secretion system and that may be products of horizontal transfer. A more diverse region is composed of genes for secreted proteins and genes that we infer to be original components of the E. coli genome. This genetic mosaic seems to be differentially affected by selection and mutation. Our results suggest that recombination and selection may be breaking this structure so that different elements are, at best, weakly coupled in their evolution. These observations suggest that the units of selection are not the complete island, but rather, much smaller units that comprise the island.