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：
Tim van Opijnen
金额：
$ 23.48万
依托单位：
BOSTON COLLEGE
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

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（应用程序提供）：来自同一物种的细菌菌株之间的基因组变异可能是如此之大，以至于没有两个基因组可能包含相同的含量。这导致了物种的核心基因组（物种所有成员共享的基因库）和泛基因组（物种的全球基因曲目）之间的区别。因此，尽管菌株属于同一物种，但基因组含量的存在和不存在的差异意味着它们可能无法以相同的方式发挥作用，可能会影响包括细菌病毒在内的各种表型。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，可以在生活的不同领域中观察到。然而，由于与进行全基因组和全物种实验相关的困难，迄今为止，全面的研究都被忽略了。通过引入全基因组工具转座子测序（TN-Seq，我们开发的一种方法），现在可以将遗传背景的影响在基因组范围的尺度上解开遗传背景的影响，并且对细菌病原体的物种范围的水平。在这里，我们关注细菌肺炎肺炎链球菌是鼻咽的常见占用者，其泛基因组比核心基因组大3倍，以及全球疾病的主要病因，导致数以百万个侵入性的肺炎性肺炎球菌疾病，每年约150万次死亡。我们假设一组潜水员的基因，途径和小型非编码RNA（NCRNA）参与病毒，并且由于遗传背景的差异这些成分及其所起的作用仅在跨菌株中部分保守。我们建议详细确定50个肺炎链球菌菌株的病毒潜力，覆盖92％的泛基因组，从而揭示对于宿主殖民化和疾病诱导最重要的基因组模式。这将使我们能够预测：1）基因型的病毒水平，以及2）基因型进化较高病毒水平的可能性。因此，该提议适合专业实验室的长期目标，即了解细菌如何在物种水平上诱导疾病，以便应用这些知识以对菌株的潜在病毒进行预测，并且设计整个物种的抗菌策略。

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：
Cell host & microbe
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