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

项目摘要/摘要 我们对细菌基因组的大规模生物信息学分析表明，10%-20%的细菌含有不同的 活跃的Tn7样元素。我们发现许多以前未解之谜的致病岛被解释 这些因素表明，它们是重要的、被低估的 细菌种类繁多。 在这笔赠款中，我们将开发计算方法来列举、分类和表征TN7- 类似的元素，将提供对它们在 细菌中抗生素耐药的发病机制和获得。这包括确定基因座 Tn7类分子形成基因组岛的地方，它们动员的遗传信息，以及基因 与动员相关的产品。我们将使用这些信息来开发基于以下内容的新工具 这些元素可以有效地设计不同类型的重要细菌。这将包括以下工具 将遗传信息插入到细菌染色体上保守的中性位置 效率，包括新出现的病原体和缺乏有效基因的共生菌 工具。 与公共健康的相关性：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方法和策略，以限制更严重的病原体的演变。 公共健康也将得到服务，因为我们将开发一种重要的新基因组 将广泛应用于细菌以及可能的其他种类的 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.