Collaborative Research: Adaptive Bridge or Barrier? The Impact of Horizontal Transfer on Genetic Evolution

协作研究：自适应桥梁还是障碍？

• 批准号: 2142718
• 负责人: Benjamin Kerr
• 金额: $ 79.95万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2142718&HistoricalAwards=false
• 关键词: Collaborative; Research; Adaptive; Bridge; Barrier

Bacteria are an essential part of life on earth, but we do not really understand how they rapidly adapt to new environments. Genes in bacteria are not only inherited from parent to offspring but can also transfer between different species. This “horizontal gene transfer” is often caused by small genetic elements called conjugative plasmids. These plasmids carry the machinery to move copies of themselves into new bacterial cells. A gene on one of these plasmids can inhabit very different host cells over time. A mutation in this gene may then have different effects in each host. This means genes could evolve differently during parent offspring transmission than when they are transferred horizontally between species. This project combines mathematical models and experiments with different bacterial species to measure the effect of horizontal transfer on the evolution of an antibiotic resistance gene and determine how that influences adaptation to changing conditions. Because antibiotic resistance genes are often located on these plasmids, this will aid in combating the evolution of drug resistance. Additional broader impacts include the development of learning tools and a new undergraduate course that will provide authentic research experiences for students. This project has three research aims. First, the researchers will propagate communities with combinations of three bacterial species (Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae) and monitor the evolution of a plasmid-borne gene coding for resistance to beta-lactam antibiotics. Horizontal gene transfer will be manipulated during this process to determine the role of transfer between species in evolution of drug resistance. Second, genetically engineered bacteria will be used to determine why certain mutational sets are favored during horizontal transfer. Mathematically modeling of the results will produce predictions about whether horizontal transfer speeds or hinders the evolution of drug resistance. Third, the researchers will build a computational model to incorporate more realistic features of microbial communities, including more complex environments, migration, and competition between different bacterial species. This model will be tested in live bacterial communities with horizontal transfer turned on or off through plasmid engineering. Overall, this project will elucidate the role that horizontal genetic inheritance plays in the evolution of bacterial communities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

细菌是地球上生命的重要组成部分，但我们并不真正了解它们是如何迅速适应新环境的。细菌中的基因不仅可以从亲代遗传给后代，而且可以在不同物种之间转移。这种“水平基因转移”通常是由称为共轭质粒的小遗传元件引起的。这些质粒携带着将自身复制到新的细菌细胞中的机制。随着时间的推移，这些质粒中的一个基因可以寄居在非常不同的宿主细胞中。这种基因的突变可能对每个宿主产生不同的影响。这意味着基因在亲代传递过程中的进化可能与在物种间水平传递时的进化不同。该项目结合了不同细菌种类的数学模型和实验，以测量水平转移对抗生素抗性基因进化的影响，并确定这如何影响对不断变化的条件的适应。由于抗生素耐药基因通常位于这些质粒上，这将有助于对抗耐药性的演变。其他更广泛的影响包括学习工具的发展和新的本科课程，将为学生提供真实的研究经验。这个项目有三个研究目的。首先，研究人员将用三种细菌（大肠杆菌、肠炎沙门氏菌和肺炎克雷伯菌）的组合繁殖群落，并监测一种编码对-内酰胺类抗生素耐药的质粒携带基因的进化。在此过程中，将操纵水平基因转移，以确定物种间转移在耐药性进化中的作用。其次，基因工程细菌将用于确定为什么某些突变集在水平转移过程中更受青睐。对结果进行数学建模，可以预测水平转移是否会加速或阻碍耐药性的进化。第三，研究人员将建立一个计算模型，以纳入更现实的微生物群落特征，包括更复杂的环境、迁移和不同细菌物种之间的竞争。该模型将通过质粒工程在水平转移打开或关闭的活细菌群落中进行测试。总的来说，本项目将阐明水平遗传在细菌群落进化中的作用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Evolutionary "Crowdsourcing": Alignment of Fitness Landscapes Allows for Cross-species Adaptation of a Horizontally Transferred Gene.

• DOI: 10.1093/molbev/msad237
• 发表时间: 2023-11-03
• 期刊: MOLECULAR BIOLOGY AND EVOLUTION
• 影响因子: 10.7
• 作者: Kosterlitz, Olivia;Grassi, Nathan;Werner, Bailey;Mcgee, Ryan Seamus;Top, Eva M.;Kerr, Benjamin
• 通讯作者: Kerr, Benjamin

Guidelines for the estimation and reporting of plasmid conjugation rates

质粒结合率估计和报告指南

• DOI: 10.1016/j.plasmid.2023.102685
• 发表时间: 2023
• 期刊: Plasmid
• 影响因子: 2.6
• 作者: Kosterlitz, Olivia;Huisman, Jana S.
• 通讯作者: Huisman, Jana S.

Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis.

• DOI: 10.1371/journal.pbio.3001732
• 发表时间: 2022-07
• 期刊: PLOS BIOLOGY
• 影响因子: 9.8
• 作者: Kosterlitz, Olivia;Tirado, Adamaris Muniz;Wate, Claire;Elg, Clint;Bozic, Ivana;Top, Eva M.;Kerr, Benjamin
• 通讯作者: Kerr, Benjamin