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.

微生物通常栖息于多样群落中，其群落组成的变化对健康、工业与环境均具有关键意义。然而，在这类复杂环境中，驱动某一菌株竞争性替代另一菌株的机制仍未得到充分阐明。本研究构建了通用生态学模型，揭示了菌株替代的一般性原则：生态入侵依赖于弱资源竞争，而菌株替代则依赖于强干扰竞争——例如通过细菌素（bacteriocin）的产生实现。随后，我们通过基因工程改造大肠杆菌（Escherichia coli），以操控资源竞争与干扰竞争两种过程，对上述预测进行了实验验证。进一步地，我们依托所提出的生态学原则，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更广泛群落的弱资源竞争（即低“养分阻断”）。本研究确立了微生物组（microbiome）中生态成功的一般性规则，并为靶向替代有害细菌提供了可行思路。