Predicting species-wide virulence for a bacterial pathogen with a large pan-genome
预测具有大型泛基因组的细菌病原体的物种范围毒力
基本信息
- 批准号:9199847
- 负责人:
- 金额:$ 23.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-01-05 至 2018-12-31
- 项目状态:已结题
- 来源:
- 关键词:AffectBacteriaCessation of lifeCharacteristicsClinicalCluster AnalysisDataDevelopmentDiseaseEpithelial CellsEtiologyGene PoolGenesGeneticGenomeGenomicsGenotypeGoalsGrowthInfectionInvadedKnowledgeLeadLibrariesLifeLungMassive Parallel SequencingMeasuresMethodsMusMutagenesisNasopharynxOrganismPathway interactionsPatternPhenotypePlayPneumococcal InfectionsPneumoniaProcessRoleSamplingStreptococcus pneumoniaeTechniquesUntranslated RNAVacuumVariantVirulenceadaptive learningantimicrobialdesignexperimental studyfitnessgenetic elementgenome-widegenomic variationhigh throughput analysisin vivokillingsmembermouse modelneglectnovelpan-genomepathogenpathogenic bacteriapublic health relevancespecies differencesuccesstool
项目摘要
DESCRIPTION (provided by applicant): Genomic variation between bacterial strains from the same species can be so large that no two genomes may contain the same content. This has lead to a distinction between a species' core-genome (the pool of genes shared by all members of a species) and pan-genome (a species' global gene repertoire). Consequently, although strains belong to the same species, differences in the presence and absence of genomic content means that they may not function in the same manner, potentially affecting all sorts of phenotypes including bacterial virulence. A growing body of evidence suggests that the genetic background effect is actually a broad phenomenon that can be observed in different domains of life. However, due to difficulties associated with performing both genome-wide as well as species-wide experiments, comprehensive studies have so far been neglected. With the introduction of the genome- wide tool transposon sequencing (Tn-seq, a method we developed), it has now become feasible to untangle the influence of the genetic-background on a genome-wide scale and a species-wide level for a bacterial pathogen. Here we focus on the bacterium Streptococcus pneumoniae a common occupant of the nasopharynx, with a pan-genome 3-fold larger than the core-genome, and a major etiology of illness worldwide causing tens of millions of episodes of invasive pneumococcal disease and ~1.5 million deaths each year. We hypothesize that a diverse set of genes, pathways and small non-coding RNAs (ncRNAs), are involved in virulence and due to differences in genetic-background these components and the roles they play are only partially conserved across strains. We propose to determine in detail the virulence potential for 50 S. pneumoniae strains, covering 92% of the pan-genome, thereby unraveling the genomic-patterns that are most important for host-colonization and disease induction. This will enable us to predict: 1) the virulence-level of a genotype, and 2) a genotype's likelihood to evolve a higher virulence-level. Thereby this proposal fits into the major
long-term goal of the lab, which is to understand how bacteria induce disease on a species-wide level in order to apply this knowledge to enable predictions on a strain's potential virulence, and
design species-wide antimicrobial strategies.
描述(由申请人提供):来自同一物种的细菌菌株之间的基因组变异可能如此之大,以至于没有两个基因组可能包含相同的内容,这导致了物种核心基因组(物种共享的基因库)之间的区别。一个物种的所有成员)和泛基因组(一个物种的全局基因库测试),尽管菌株属于同一物种,但基因组内容存在和不存在的差异意味着它们可能不会以相同的方式发挥作用。影响着各方面越来越多的证据表明,遗传背景效应实际上是一种广泛的现象,可以在生命的不同领域观察到。然而,由于进行全基因组和物种范围的实验存在困难。迄今为止,随着全基因组工具转座子测序(Tn-seq,我们开发的一种方法)的引入,现在已经可以理清遗传背景对全基因组的影响。规模和物种范围的水平在这里,我们重点关注鼻咽部常见的肺炎链球菌,其全基因组比核心基因组大 3 倍,是全球疾病的主要病因,导致数千万次侵袭性肺炎发作。我们发现,多种基因、通路和小非编码 RNA (ncRNA) 与毒力有关,每年导致肺炎球菌疾病和约 150 万人死亡。由于遗传背景的差异,这些成分及其所发挥的作用在不同菌株之间仅部分保守,我们建议详细确定 50 种肺炎链球菌菌株的毒力潜力,涵盖 92% 的全基因组,从而揭开其致病性。对宿主定植和疾病诱导最重要的基因组模式这将使我们能够预测:1)基因型的毒力水平,2)基因型进化出更高水平的可能性。因此,该提议符合主要内容。
实验室的长期目标是了解细菌如何在物种范围内诱发疾病,以便应用这些知识来预测菌株的潜在毒力,以及
设计物种范围的抗菌策略。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts.
- DOI:10.1016/j.chom.2019.04.012
- 发表时间:2019-06
- 期刊:
- 影响因子:30.3
- 作者:Hannah M. Rowe;E. Karlsson;H. Echlin;Ti‐Cheng Chang;Lei Wang;T. van Opijnen;S. Pounds;S. Schultz‐Cherry;J. Rosch
- 通讯作者:Hannah M. Rowe;E. Karlsson;H. Echlin;Ti‐Cheng Chang;Lei Wang;T. van Opijnen;S. Pounds;S. Schultz‐Cherry;J. Rosch
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Tim van Opijnen其他文献
Tim van Opijnen的其他文献
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A blind source separation approach for deconvolution of bulk transcriptional data leads to early detection of ATF cell-states in complex bacterial populations, in vitro and in vivo
用于批量转录数据去卷积的盲源分离方法可以在体外和体内早期检测复杂细菌群体中的 ATF 细胞状态
- 批准号:
10703357 - 财政年份:2022
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A priori adaptive evolution predictions for antibiotic resistance through genome-wide network analyses and machine learning
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10155396 - 财政年份:2020
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