Strain displacement in microbiomes via ecological competition

Microbes commonly live in diverse communities where changes in composition can be critical for health, industry and the environment. Yet, what enables one strain to competitively replace another in these complex conditions remains poorly understood. Here, we develop a general ecological model, which reveals general principles of strain displacement. Ecological invasion rests upon weak resource competition while displacement rests upon strong interference competition e.g. via bacteriocin production. We test these predictions by genetically-engineering Escherichia coli to manipulate both resource and interference competition. We then use our ecological principles to identify strains that out-compete multidrug-resistant clinical isolates via a combination of low resource, but high interference, competition. Experiments with diverse human gut symbionts reveal that displacement also relies on low resource competition with the broader community (low ‘nutrient blocking’). Our work establishes general rules for ecological success in microbiomes and suggests ways to perform targeted displacement of problematic bacteria.微生物多栖息于复杂多样的群落中，群落组成的改变对人类健康、工业应用及生态环境均具有至关重要的意义。然而，在这类复杂环境中，为何某一菌株能够竞争性替代另一菌株，目前学界对此仍知之甚少。本研究构建了通用生态学模型，揭示了菌株竞争性替代的一般性规律：生态入侵依赖于较弱的资源竞争，而菌株替代则依赖于较强的干扰竞争——例如通过细菌素（bacteriocin）的产生实现。我们通过基因工程改造大肠杆菌（Escherichia coli）以调控资源竞争与干扰竞争，以此验证上述理论预测。随后，我们基于所提出的生态学原理，通过结合低资源竞争与高干扰竞争的策略，筛选出能够竞争性击败多重耐药临床分离株的菌株。针对多种人类肠道共生菌的实验表明，菌株替代同样依赖于与群落整体间的低资源竞争（即低水平的“营养阻断”）。本研究确立了微生物组中生态适配成功的一般性规则，并为针对性清除有害菌株提供了可行路径。