BBSRC-NSF/BIO - The impact of public versus private metabolism on the stability of microbial communities within natural hosts

当有一种无需开发的替代方案时，为什么微生物会参与可开发利用的营养物合作消耗？我们的建议将通过合成生物学，数学建模和体内微生物群落实验的结合来回答这个基本的尚未解决的问题。微生物在生态系统功能和宏观生物的健康中起着至关重要的作用。它们在从动物内脏到土壤等环境中与多细胞生物形成有益的关系，并可用于降解工业废物或生产有用的化学品。但它们也会造成毁灭性的破坏，破坏我们的食物来源，消灭关键的植物物种，从而阻止对数亿吨二氧化碳的吸收。微生物不是孤立存在的，相反，它们形成了由不同菌株和物种组成的复杂群落，其中个体参与复杂的合作和竞争相互作用。然而，我们对这些相互作用如何改变社区的功能和稳定性缺乏全面的了解。这对于预测促进自然环境中生存和生长的微生物策略的进化至关重要。为了生存和繁荣，微生物必须从其环境中获取营养，合作和竞争行为是微生物喂养方式的关键。获取营养物质的一种常见策略是将代谢产物分泌到外部的“公共”环境中，在它们被细胞吸收之前分解或捕获资源。代谢产物被认为是合作的公共产品，因为它们是外部产生的，因此对共享环境中的其他细胞有益。这种看似成功的策略被称为“公共代谢”，被广泛应用于各种栖息地的微生物物种，但它有两个明显的缺点。首先，公共产品很容易在被产生它们的细胞成功吸收之前就丢失在环境中。其次，公共产品可以被微生物利用，它们“欺骗”自己，不参与生产，但仍能获得回报。这些缺点会威胁到公众代谢的成功和微生物群落的稳定和功能。奇怪的是，存在一种无剥削策略，即微生物可以通过直接将营养物质带入细胞来获取营养，消化过程在细胞内“私下”进行，而不是在环境中“公开”进行。然而，尽管有这种万无一失的选择，许多微生物仍然靠公共代谢为生。我们的项目将确定为什么会出现这种情况，以及公共代谢提供了什么好处。根据初步数据，我们假设涉及公共或私人代谢的微生物摄食策略代表了两种相反的生存途径，其成功与否取决于环境。特别是，我们假设充分的空间结构环境将限制对公共代谢物的利用，从而有利于它们而不是私人代谢物。为了验证这一点，我们已经生成了两个定义良好且易于处理的合成系统，其中包括环境酵母酿酒酵母和植物病原体稻瘟病菌。这些群落将被用于实验探索不同代谢策略在其自然环境中的适合度，并评估群落的稳定性和功能。同时，我们将开发动态的、空间明确的、基因组尺度的数学模型，以产生代谢相互作用和空间结构程度如何支持群落稳定的机制理解。这将使我们能够从系统特异性观察中推断出一般原则，并对有利于合作代谢的不同类型的生物（例如宿主-病原体和微生物-微生物）和非生物（例如空间结构）条件进行分类。

Why do microorganisms engage in cooperative nutrient consumption that is open to exploitation when an exploitation-free alternative is available? Our proposal will answer this fundamental yet unanswered question through a combination of synthetic biology, mathematical modelling and in vivo microbial community experiments. Microorganisms play crucial roles in ecosystem functioning and the health of macro organisms. They form beneficial relationships with multicellular organisms, in environments ranging from animal guts to soil, and can be exploited to degrade industrial waste or produce useful chemicals. But they can also cause devastating damage by destroying our food sources and eliminating key plant species, thus preventing the absorption of hundreds of megatonnes of CO2. Microorganisms do not exist in isolation, instead they form intricate communities of diverse strains and species where individuals participate in complex cooperative and competitive interactions. However, we lack a comprehensive understanding of how these interactions alter the function and stability of the community. This is crucial for predicting the evolution of microbial strategies that promote survival and growth in natural environments.To survive and thrive, microorganisms must obtain nutrients from their environment and cooperative and competitive actions are key to the way that microbes feed. A common strategy to obtain nutrients involves secreting metabolic products into the external, "public" environment to break down or capture resources, before they are taken up into the cell. The metabolic products are considered to be cooperative public goods as they are generated externally and so benefit other cells in the shared environment. This seemingly successful strategy, termed "public metabolism", is used by a wide range of microbial species that inhabit diverse habitats, yet it has two obvious drawbacks. First, the public goods can easily be lost into the environment before they are successfully taken up by the cell that generated them. Second, the public-goods can be exploited by microbes that "cheat" by not contributing to their production but still reap the rewards. These shortcomings can threaten the success of public metabolism and the stability and functioning of microbial communities. Curiously, an exploitation-free strategy exists whereby microbes can secure nutrients by taking them directly into the cell, with digestion taking place "privately" inside the cell, instead of "publicly" in the environment. Yet despite this failsafe alternative, many microbes still feed by public metabolism. Our project will determine why this is the case and what benefits public metabolism provides.Based on preliminary data we hypothesise that microbial feeding strategies involving either public or private metabolism represent two opposing approaches to survival, the success of which is environment-dependent. In particular, we hypothesise that sufficiently spatially structured environments will limit exploitation of public-metabolisers thus favouring them over private-metabolisers.To test this, we have generated two well-defined and tractable synthetic systems involving the environmental yeast Saccharomyces cerevisiae and the plant pathogen Magnaporthe oryzae. These communities will be used to experimentally probe the fitness of different metabolic strategies in their natural environments and assess community stability and function. In parallel, we will develop dynamic, spatially explicit, genome-scale mathematical models to generate mechanistic understanding of how metabolic interactions and the degree of spatial structure support community stability. This will enable us to extrapolate general principles from the system-specific observation and to develop a classification of different types of biotic (e.g. host-pathogen and microbe-microbe) and abiotic (e.g. spatial structure) conditions that favour cooperative metabolism.