Modeling the Spatial Dynamics of Plasmid Transfer

质粒转移的空间动力学建模

• 批准号: 7385877
• 负责人: STEPHEN M. KRONE
• 金额: $ 24.21万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7385877
• 关键词: 3-Dimensional; Agar; Antibiotic Resistance; Antibiotics; Bacteria; Behavior; Biological; Biological Testing; Cells; Complex; Computer Simulation; Data; Effectiveness; Environment; Event; Evolution; Gastrointestinal tract structure; Genes; Genomics; Goals; Growth; Horizontal Gene Transfer; Human; In Vitro; Investigation; Joints; Liquid substance; Maintenance; Microbial Biofilms; Mobile Genetic Elements; Modeling; Nutrient; Organism; Pattern; Plasmids; Play; Population; Population Biology; Population Dynamics; Prevention strategy; Prokaryotic Cells; Protocols documentation; Rate; Relative (related person); Role; Silicon Dioxide; Simulate; Structure; Surface; System; Testing; Time; Work; base; chemotherapeutic agent; density; infectious disease treatment; mathematical model; microbial community; pressure; research study; segregation; tool; two-dimensional

DESCRIPTION (provided by applicant): Plasmids play a central role in the spread of antibiotic resistance among bacterial species, thereby decreasing the effectiveness of various chemotherapeutic agents for the treatment of infectious diseases. These mobile genetic elements are very common in bacteria and their horizontal transfer is key in the adaptive evolution of these organisms. The long-term goal of this study is to understand the population biology of transmissible plasmids in spatially structured microbial communities: What are the mechanisms that drive the horizontal transfer and persistence of these mobile genetic elements? Why do they persist, even in the absence of selection for any of the genes they carry? How does the spatial structure of natural microbial communities influence the ecological and evolutionary dynamics of plasmid-bacteria interactions? Therefore, a joint theoretical and experimental investigation into the role of spatial structure in the spread and persistence of self-transmissible antibiotic resistance plasmids is proposed. The specific aims of this proposal are to construct 2-dimensional and 3-dimensional stochastic cellular automata (CA) models that can be used to accurately predict the spread and persistence of natural antibiotic resistance plasmids in bacterial colonies growing on agar surfaces and in biofilms. These two settings are needed for carefully controlled comparisons with non-spatial (liquid) environments and estimation of spatially relevant parameters, and for understanding the extent to which the complex spatially heterogeneous structure of biofilms further influences plasmid transfer and persistence. To validate and/or modify the models, a sequence of parallel in vitro and in silico experiments will be performed. Each such pair of experiments will serve to (a) validate or reject the particular model as pertains to a specific biological hypothesis; (b) suggest model refinements; (c) test the biological hypothesis; and (d) formulate alternative hypotheses in the event that the original hypothesis is rejected.

描述（由申请人提供）：疟原虫在细菌物种中抗生素耐药性的传播中起核心作用，从而降低了用于治疗感染性疾病的各种化疗剂的有效性。这些移动的遗传元件在细菌中非常普遍，它们的水平转移是这些生物体适应性进化的关键。本研究的长期目标是了解空间结构微生物群落中可传播质粒的种群生物学：驱动这些移动的遗传元件水平转移和持久性的机制是什么？为什么它们会持续存在，即使它们携带的任何基因都没有被选择？天然微生物群落的空间结构如何影响质粒-细菌相互作用的生态和进化动力学？因此，提出了一个联合的理论和实验研究空间结构的自我传播的抗生素耐药质粒的传播和持久性的作用。该提案的具体目标是构建二维和三维随机细胞自动机（CA）模型，可用于准确预测琼脂表面和生物膜上生长的细菌菌落中天然抗生素耐药性质粒的传播和持久性。这两个设置需要仔细控制与非空间（液体）环境和空间相关参数的估计比较，并了解复杂的空间异质结构的生物膜进一步影响质粒转移和持久性的程度。为了验证和/或修改模型，将进行一系列平行的体外和计算机模拟实验。每对这样的实验将用于（a）验证或拒绝与特定生物学假设有关的特定模型;（B）建议模型改进;（c）测试生物学假设;以及（d）在原始假设被拒绝的情况下制定替代假设。