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，人类感染和自然环境中的微生物通常生活在空间上 结构化聚集体并彼此拮抗。毒素介导的拮抗作用 相互作用在肠道，皮肤和其他人类微生物中广泛存在，并保护它们 反对外部入侵的社区。最近的结果表明，空间结构可以强烈 影响微生物种群的进化动力学，而微生物相互作用可以 关于空间结构形成的反馈。例如，我们发现机械相互作用 在生长酵母菌菌落中的细胞中，通过减少自然选择的能力 较低的健身菌株灭绝的速度和钳工在这些人群中的扩大。 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的动力学，我们对微生物的了解中的大多数 进化动力学来自具有有限的混合液体培养物的实验 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理解 空间结构，力学和生物相互作用如何影响自适应进化 微生物种群的动力学。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，我们发现正在发展 酵母菌菌落选择以更快的琼脂表面扩张会导致细胞的显着变化 形状：细胞从椭圆形的祖先演变为被拉长，几乎是杆 就像，改变细胞在生长和分裂时机械相互作用的方式。我们假设 细长的细胞形状对于更快的膨胀有利，因为它会减少细胞 包装，这种自适应变化与基因型群集的方式有关 在导致遗传漂移增加的空间中，由于 机会事件。最近，我们表明产生毒素的微生物只能入侵景观 如果毒素产量较弱，如果其接种剂大于临界大小，并且适应性 进化可以改变对抗的动力学。我们将通过实验研究 临界接种大小对相互作用强度的依赖性，我们将研究如何 空间结构控制突变的命运，这些突变赋予对由 入侵者或居民应变。最后，我们将研究拮抗互动 在微生物中，微生物在线虫肠炎的肠道中影响侵袭动力学。 秀丽隐杆线：这些实验将帮助我们翻译在简单的实验室环境中获得的结果 入侵宿主微生物组的更复杂但更现实的动态。