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: 7381297
• 负责人: Eva M. Top
• 金额: $ 27.06万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381297
• 关键词: COBRE; UID; PROJ; EVOLUTION; ANTIBIOTIC

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NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是针对该中心的，这不是调查人员的机构。质粒是流动遗传元素，在细菌物种之间抗生素耐药性的分散体中起着核心作用，从而降低了用于治疗传染病的抗菌剂的有效性。我们研究的目的是通过实验进化研究辨别质粒进化的模式。特别是，我们旨在确定某些质粒如何发展转移和维持在广泛宿主中的能力。 64.5 kb incp-1？由于其高传递性和广泛的宿主范围，因此选择了质粒PB10作为模型系统。在污水处理厂的细菌群落中对这种质粒的天然宿主范围的检查表明，PB10转移到38种不同的物种中。这些发现还表明，质粒的宿主范围不仅取决于固有的质粒特征，还取决于原始宿主和环境参数。从这些研究中，我们发现了两个宿主，其中质粒PB10的负担更高或比大肠杆菌K12稳定。在其中一位宿主P. putida H2（PB10）的进化实验中，质粒的成本是从未携带的质粒（NA¿VE）的等源性H2菌株的成本，在1000代质粒演化后显着降低：从20％到9％或16％，取决于质粒是否常规的质粒宿主是源自源性宿主的，这是从质粒定期转移的。这些结果表明，质粒编码的自适应变化是造成这种巨大质粒宿主适应的原因，并且正在研究分子基础。同时，将三个天然存在的Incp-1质粒的基因组序列与已知的Incp-1质粒进行了比较。相比之下，所有其他所有测序的Incp-1？质粒，质粒PB3的Oriv区域不会被转座子中断，从而为这些混杂质粒的进化史提供了新的启示。