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1.
The phylogenetic profile of a gene is a reflection of its evolutionary history and can be defined as the differential presence or absence of a gene in a set of reference genomes. It has been employed to facilitate the prediction of gene functions. However, the hypothesis that the application of this concept can also facilitate the discovery of bacterial virulence factors has not been fully examined. In this paper, we test this hypothesis and report a computational pipeline designed to identify previously unknown bacterial virulence genes using group B streptococcus (GBS) as an example. Phylogenetic profiles of all GBS genes across 467 bacterial reference genomes were determined by candidate-against-all BLAST searches,which were then used to identify candidate virulence genes by machine learning models. Evaluation experiments with known GBS virulence genes suggested good functional and model consistency in cross-validation analyses (areas under ROC curve, 0.80 and 0.98 respectively). Inspection of the top-10 genes in each of the 15 virulence functional groups revealed at least 15 (of 119) homologous genes implicated in virulence in other human pathogens but previously unrecognized as potential virulence genes in GBS. Among these highly-ranked genes, many encode hypothetical proteins with possible roles in GBS virulence. Thus, our approach has led to the identification of a set of genes potentially affecting the virulence potential of GBS, which are potential candidates for further in vitro and in vivo investigations. This computational pipeline can also be extended to in silico analysis of virulence determinants of other bacterial pathogens.  相似文献   

2.
Abstract Inoculum concentration, length of incubation period and passages on leaves of potato R–genotypes were found to influence the detectability of virulence genes in Phytophthora infestans.
At lower inoculum concentrations, only a few virulence genes were detected, these were usually 1 and 4. Coupled with an increase of the inoculum dose a gradual increase was found in the number of detected genes and their multiple combinations. An increased incubation time also resulted in the detection of additional virulence genes and their combinations. Two successive passages on respective potato R-genotypes produced a 2--3 fold rise in the number of detected genes.
To explain this phenomenon, a hypothesis has been proposed which suggests that for a virulence gene to be detected, certain infection thresholds have to be reached, which may be different for particular differential host genotypes or virulence genes.  相似文献   

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V. cholerae strains of different origin have been studied for the presence of cholera toxin genes (vct), the proximal part of the virulence cassette including genes zot, ace and orfU, as well as neuraminidase genes (neu), in their genomes with the use of molecular DNA probes. The possibility, in principle, for some strains to lose only a part of their virulence cassette (gene vct), while retaining its proximal part has been shown. In most cases such strains are isolated from patients with diarrhea of different severity and may probably play some etiological role, provided that the expression of the genes of additional toxins of the virulence cassette occurs. The gene expressing neuraminidase which facilitates the penetration of cholera toxin into the epithelial cells of the intestine is always present in vct+ strains and may be absent in vct- strains. The absence of genetic relationship between neuraminidases in V. cholerae O139 and V. cholerae O1 and non-O1 (non-O139) has been confirmed. The problems in connection with the integration and deletion of genetic determinants of V. cholerae virulence factors are discussed.  相似文献   

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Streptococcus uberis is an important pathogen that has been implicated in bovine mastitis but the virulence factors associated with pathogenesis are not well understood. The aim of this work was to examine 11 putative and known virulence-associated genes by PCR in 78 S. uberis strains isolated from infected animals in Argentina. Additionally, the distribution of virulence patterns over various herds was determined. Not all genes were present in the strains but all of the detected virulence-associated genes were present in combination. Forty-seven (60.3%) isolates carried seven to 10 virulence-associated genes. Further analysis revealed 58 virulence patterns. Different patterns were found within the same herd and among herds, demonstrating that strains with different virulence patterns were able to cause mastitis. Despite the large number of strains with different virulence patterns, strains with identical patterns was found. Detection of virulence-associated genes in individual S. uberis strains isolated from infected animals revealed one to 10 virulence genes. This may indicate that other virulence factors could be involved. The present study reveals the occurrence and distribution of 11 virulence-associated genes among S. uberis isolates from bovine mastitis in various herds and contributes to a better understanding of the pathogenicity of this bacterium.  相似文献   

5.
姚潇  黄留玉  杨伯伦  苏国富 《遗传》2002,24(6):721-726
信号标签诱变技术是以整个基因组为基础的研究病原体致病机制,可在体内对毒力基因进行高通量筛选的一种新方法。近几年应用该技术已对十多种病原微生物进行了筛选。这些筛选中除了找到已知的毒力基因外,还都鉴定到了未知的毒力因子。本文就该技术的原理、优缺点、应用的必要条件、技术的改进及应用该技术鉴定到的毒力基因等作一综述。 A Novel Approach to Study Pathogenesis of Pathogens in vivo——Signature-tagged Mutagenesis YAO Xiao1,2,HUANG Liu-yu1,YANG Bo-lun2,SU Guo-fu1 1.Beijing Institute of Biotechnoloy,Beijing 100071,China; 2.College of Environmental and Chemical Engineering,Xi'an Jiaotong University,Xi'an 710049,China Abstract:Signature-tagged mutagenesis (STM) is a novel approach to study pathogenesis of pathogens and to screen virulence genes with high throughput in vivo,which is based on whole genome of pathogen in question.In resent years,more than ten species of microbial pathogens have been screened with this technology.There are also unknown virulence factors being identified with exception of known virulence genes identified in all these screens.This article reviews the principle,advantages and current limitations,the requirements,modifications of STM,and to date virulence genes identified by this technology. Key words:signature-tagged mutagenesis;virulence genes;pathogens;in vivo  相似文献   

6.
Many proteins from plant pathogens affecting the interaction with the host plant have dual functions: they promote virulence on the host species and they function as avirulence determinants by eliciting defense reactions in host cultivars expressing the appropriate resistance genes. In viruses all proteins encoded by the small genomes can be expected to be essential for viral development in the host. However, in different plants surveillance systems have evolved that are able to recognize most of these proteins. Bacteria and fungi have specialized pathogenicity and virulence genes. Many of the latter were originally identified through the resistance gene-dependent elicitor activity of their products. Their role in virulence only became apparent when they were inactivated or transferred to different microbes or after their ectopic expression in host plants. Many microbes appear to maintain these genes despite their disadvantageous effect, introducing only few mutations to abolish the interaction of their products with the plant recognition system. This has been interpreted as been indicative of a virulence function of the gene products that is not impaired by the mutations. Alternatively, in particular in bacteria there is now evidence that pathogenicity was acquired through horizontal gene transfer. Genes supporting virulence in the donor organism's original host appear to have traveled along. Being gratuitous in the new situation, they may have been inactivated without loss of any beneficial function for the pathogen.  相似文献   

7.
The human pathogen Pseudomonas aeruginosa has been shown previously to use similar virulence factors when infecting mammalian hosts or Dictyostelium amoebae. Here we randomly mutagenized a clinical isolate of P. aeruginosa , and identified mutants with attenuated virulence towards Dictyostelium . These mutant strains also exhibited a strong decrease in virulence when infecting Drosophila and mice, confirming that P. aeruginosa makes use of similar virulence traits to confront these very different hosts. Further characterization of these bacterial mutants showed that TrpD is important for the induction of the quorum-sensing circuit, while PchH and PchI are involved in the induction of the type III secretion system. These results demonstrate the usefulness and the relevance of the Dictyostelium host model to identify and analyse new virulence genes in P. aeruginosa .  相似文献   

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