COBRE: UID: PROJ 2: EVOLUTION OF ANTIBIOTIC RESISTANCE PLASMIDS

COBRE：UID：项目 2：抗生素抗性质粒的进化

• 批准号: 7720636
• 负责人: Eva M. Top
• 金额: $ 25.46万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720636
• 关键词: Antibiotic Resistance; Biological Models; Characteristics; Communities; Computer Retrieval of Information on Scientific Projects Database; Effectiveness; Escherichia coli K12; Evolution; Funding; Generations; Grant; Institution; Light; Mobile Genetic Elements; Molecular; Pattern; Plants; Plasmids; Play; Range; Recording of previous events; Research; Research Personnel; Resources; Role; Source; United States National Institutes of Health; antimicrobial drug; base; cost; genome sequencing; infectious disease treatment; research study; sewage treatment

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Plasmids are mobile genetic elements that play a central role in the dispersion of antibiotic resistance among bacterial species, thereby decreasing the effectiveness of antimicrobial agents used for the treatment of infectious diseases. The objective of our research is to discern patterns of plasmid evolution through experimental evolution studies. In particular, we aim to determine how some plasmids have evolved the ability to transfer and be maintained in a wide range of hosts. The 64.5 kb IncP-1? plasmid pB10 was chosen as a model system because of its high transferability and broad host-range. An examination of the natural host-range of this plasmid in the bacterial community of a sewage treatment plant showed that pB10 transferred to 38 distinct species. These findings also suggested that the host-range of a plasmid was not only determined by intrinsic plasmid characteristics but by the original host and the environmental parameters. From these studies we found two hosts in which plasmid pB10 presents a higher burden or is less stable than in E. coli K12. In an evolution experiment with one of these hosts, P. putida H2 (pB10), the cost of the plasmid to an isogenic H2 strain that had never carried the plasmid before (na¿ve), was significantly decreased after 1000 generations of plasmid evolution: from 20% to 9% or 16%, depending on whether or not the plasmid was regularly transferred between isogenic hosts. These results indicate that plasmid-encoded adaptive changes were responsible for this drastic plasmid-host adaptation, and the molecular basis is being examined. In parallel, the genome sequences of three naturally occurring IncP-1 plasmids were compared with those of known IncP-1 plasmids. In contrast two all other sequenced IncP-1? plasmids, the oriV region of plasmid pB3 is not interrupted by transposons, shedding new light on the evolutionary history of these promiscuous plasmids.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 质粒是可移动的遗传元件，在细菌物种之间抗生素耐药性的分散中发挥着核心作用，从而降低了用于治疗传染病的抗菌药物的有效性。我们研究的目的是通过实验进化研究来辨别质粒进化的模式。特别是，我们的目标是确定一些质粒如何进化出在多种宿主中转移和维持的能力。 64.5 kb IncP-1？质粒pB10因其高可转移性和广泛的宿主范围而被选为模型系统。对污水处理厂细菌群落中该质粒的自然宿主范围的检查表明，pB10 转移到了 38 个不同的物种。这些发现还表明，质粒的宿主范围不仅取决于质粒的内在特征，还取决于原始宿主和环境参数。从这些研究中，我们发现了两种宿主，其中质粒 pB10 比大肠杆菌 K12 具有更高的负担或稳定性更低。在使用其中一种宿主恶臭假单胞菌 H2 (pB10) 进行的进化实验中，对于以前从未携带过该质粒的同基因 H2 菌株（幼稚）来说，质粒成本在 1000 代质粒进化后显着降低：从 20% 降至 9% 或 16%，具体取决于质粒是否在同基因宿主之间定期转移。这些结果表明，质粒编码的适应性变化是造成这种剧烈的质粒-宿主适应的原因，并且其分子基础正在研究中。同时，将三种天然存在的 IncP-1 质粒的基因组序列与已知 IncP-1 质粒的基因组序列进行了比较。相比之下，所有其他两个测序的 IncP-1？与其他质粒相比，质粒 pB3 的 oriV 区域没有被转座子打断，这为了解这些混杂质粒的进化史提供了新的线索。