Evolutionary dynamics of dense, spatially structured, and antagonistic microbial populations

密集、空间结构和对抗性微生物种群的进化动力学

• 批准号: 10684081
• 负责人: Andrea Giometto
• 金额: $ 38.15万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684081
• 关键词: Affect; Agar; Antibiosis; Biological; Caenorhabditis elegans; Cell Communication; Cell Shape; Cells; Chemicals; Communities; Dependence; Engineering; Environment; Event; Evolution; Feedback; Gene Frequency; Genetic Drift; Genotype; Health; Human; Human Microbiome; Infection; Infection prevention; Invaded; Laboratories; Liquid substance; Mechanics; Mediating; Microbe; Mutation; Natural Selections; Nematoda; Penetration; Population; Replacement Therapy; Resistance; Rod; Shapes; Skin; Structure; Surface; Toxin; Translating; Work; Yeasts; antagonist; design; experimental study; fitness; host microbiome; interest; mathematical model; microbial; microbial community; microbiome; microorganism interaction; pathogen; pressure; soft tissue; synthetic biology

Abstract Microbes in host microbiomes, human infections and the natural environment often live in spatially structured aggregates and interact antagonistically with each other. Toxin-mediated antagonistic interactions are widespread in the gut, skin, and other human microbiomes, and protect these communities against external invasion. Recent results suggest that spatial structure can strongly affect the evolutionary dynamics of microbial populations, and, in turn, microbial interactions can feedback on the formation of spatial structure. For example, we found that mechanical interactions among dividing cells in growing yeast colonies reduce the power of natural selection by reducing the rates at which lower fitness strains go extinct and fitter ones expand in these populations. Despite spatial structure and microbial interactions have a strong impact on the evolutionary dynamics of microbes relevant for human health, most of what we know about microbial evolutionary dynamics comes from experiments with well-mixed liquid cultures with limited interactions among cells. To fill this gap, my group is interested in understanding quantitatively how spatial structure, mechanics and biological interactions impact the adaptive evolutionary dynamics of microbial populations. We approach this question via experimental evolution, synthetic biology, and mathematical modeling. In preliminary experiments, we found that evolving yeast colonies selecting for faster expansion on agar surfaces results in notable changes in cell shape: cells evolved from an ellipsoidally shaped ancestor to being elongated and almost rod- like, changing the way cells interact mechanically when growing and dividing. We hypothesize that an elongated cell shape is advantageous for faster expansion because it reduces cell packing, and that this adaptive change is associated with changes in the way genotypes cluster in space leading to increased genetic drift, the temporal change in allele frequencies due to chance events. Recently, we showed that a toxin-producing microbe can only invade a landscape occupied by a weaker toxin-producer if its inoculum is larger than a critical size, and that adaptive evolution can alter the dynamics of antagonism. We will experimentally investigate the dependence of the critical inoculum size on the strength of the interaction, and we will study how spatial structure controls the fate of mutations that confer resistance to the toxin produced by either the invader or resident strain. Finally, we will investigate how antagonistic interactions among microbes affect the dynamics of invasion in the gut of the nematode Caenorhabditis elegans: these experiments will help us translate results obtained in simple laboratory settings to the more complicated but more realistic dynamics of invasion of a host microbiome.

抽象的 宿主微生物组、人类感染和自然环境中的微生物通常生活在空间中 结构化聚集体并相互拮抗地相互作用。毒素介导的拮抗剂 相互作用在肠道、皮肤和其他人类微生物组中广泛存在，并保护这些微生物 社区抵御外来入侵。最近的结果表明，空间结构可以强烈地 影响微生物种群的进化动态，反过来，微生物相互作用可以 空间结构形成的反馈。例如，我们发现机械相互作用 正在生长的酵母菌落中的分裂细胞之间通过减少 在这些人群中，适应性较差的品种灭绝的速度和适应性强的品种扩张的速度。 尽管空间结构和微生物相互作用对进化有很大影响 与人类健康相关的微生物动态，我们对微生物的大部分了解 进化动力学来自于充分混合的液体培养物的实验，其有限的 细胞之间的相互作用。为了填补这一空白，我的小组有兴趣定量地理解 空间结构、力学和生物相互作用如何影响适应性进化 微生物种群的动态。我们通过实验进化来解决这个问题， 合成生物学和数学建模。在初步实验中，我们发现进化 酵母菌落选择在琼脂表面上快速扩张会导致细胞发生显着变化 形状：细胞从椭圆形祖先进化为细长且几乎呈杆状 比如，改变细胞生长和分裂时机械相互作用的方式。我们假设 细长的细胞形状有利于更快的扩张，因为它减少了细胞 包装，并且这种适应性变化与基因型聚类方式的变化相关 在空间中导致遗传漂变增加，等位基因频率的时间变化是由于 偶然事件。最近，我们证明产生毒素的微生物只能侵入景观 如果接种量大于临界尺寸，则被较弱的毒素产生者占据，并且适应性 进化可以改变对抗的动态。我们将通过实验研究 临界接种量对相互作用强度的依赖性，我们将研究如何 空间结构控制着突变的命运，这些突变赋予了对由 入侵者或常驻菌株。最后，我们将研究拮抗相互作用如何 微生物之间影响线虫肠道入侵动态 线虫：这些实验将帮助我们将在简单实验室环境中获得的结果转化为 宿主微生物组入侵的更复杂但更现实的动态。