Building a Comprehensive Discovery System for Understanding Bacterial Multidrug Resistance and Pathogenesis Using Tn7-like Elements

项目概要/摘要 我们对细菌基因组进行的大规模生物信息学分析表明，10-20%的细菌基因组含有不同的 活性Tn 7样元素。我们发现，许多以前神秘的致病岛解释 这些因素表明，它们是重要的和未得到充分重视的交流工具， 不同的细菌种类。 在这项资助中，我们将开发计算方法来枚举，分类和表征Tn 7- 类似的元素，这将提供一个全面的了解他们的作用， 致病机理和细菌抗生素耐药性的获得。这包括确定 其中Tn 7样元件形成基因组岛，它们动员的遗传信息和基因 与动员有关的产品。我们将利用这些信息开发基于以下方面的新工具： 这些元素有效地工程化不同类型的重要细菌。这将包括工具， 将遗传信息插入到细菌染色体中的保守中性位点， 效率，包括新出现的病原体和缺乏有效遗传 工具. 与公共卫生的相关性：我们将确定允许进化的分子机制。 新出现的病原体和多重耐药细菌通过遗传信息的转移。 这将导致更好的治疗和策略，以限制更严重的病原体的演变。 公共卫生也将得到服务，因为我们将开发一个重要的新基因组 这种修饰技术将广泛适用于细菌和可能的其他种类的细菌。 有机体

Project Summary / Abstract Our large-scale bioinformatics analyses of bacterial genomes indicate that 10-20% contain diverse active Tn7-like elements. We find that many previously enigmatic pathogenicity islands are explained by these elements suggesting they are important and underappreciated vehicles of exchange across diverse bacterial species. In this grant, we will develop computational methods to enumerate, classify and characterize Tn7- like elements which will provide a comprehensive understanding of their roles in the evolution of pathogenesis and acquisition of antibiotic resistance in bacteria. This includes determining the loci where Tn7-like elements form genomic islands, the genetic information they mobilize, and the gene products associated with mobilization. We will use this information to develop new tools based on these elements to efficiently engineer diverse types of important bacteria. This will include tools to insert genetic information into conserved neutral sites in the chromosomes of bacteria at high efficiency, including new and emerging pathogens and commensal bacteria that lack efficient genetic tools. Relevance to Public Health: We will determine the molecular mechanisms that allow the evolution of emerging pathogens and multi drug resistant bacteria though the transfer of genetic information. This will lead to better treatments and strategies to limit the evolution of more serious pathogens. Public health will also be served because we will be developing an important new genome modification technique that will be broadly applicable in bacteria and possibly other kinds of organisms.