Managing the competition: How do burying beetles and microbes sustainably coexist in competition over shared resources?

抗生素耐药性（AMR）是当今社会面临的最重要的公共卫生问题之一。抗生素的不适当使用加速了细菌产生耐药性的速度，新抗菌剂的开发非常昂贵和耗时，几乎已经停止。因此，我们需要开发更好的方法来可持续地利用现有和未来的抗菌药物。然而，在管理耐药性的最佳方法上缺乏共识，特别是对于细菌。哪种耐药性管理策略最有效？降低处方率是否最有效，或者抗菌药物是否应该联合使用，如果是，什么联合使用？在临床环境中很难解决这些问题，目前很少有相关的实验系统在临床试验之外验证耐药管理策略。在这里，我们提出了一种新的方法来解决这些问题：使用生物体，其中细菌和其他微生物的管理是其自然历史的一个基本组成部分，以阐明最有效的战略，以打击抗菌素耐药性。埋葬甲虫完全符合要求。它们处理老鼠等小型脊椎动物的尸体以养育它们的后代，并且在无脊椎动物中具有广泛的，复杂的父母照顾。除了像鸟类一样喂养它们的后代（埋葬甲虫幼虫乞求喂食，父母则通过杀死食物-死老鼠来回应），它们还产生抗菌分泌物来对抗微生物的竞争，特别是细菌。我们在这里最感兴趣的是后一种形式的父母照顾。由于有证据表明，埋葬甲虫已经提供了约1亿年的照顾和管理来自微生物的竞争，因此探索它们使用的抗性管理策略可能会带来可观的回报。我们方法的特别新奇在于使用实验进化来观察甲虫和细菌如何应对彼此增加的选择压力。因此，我们可以观察行动中的进化，并直接测试不同抗性管理策略的相对效率。特别是，我们将用我们将在实验室中产生的耐药细菌挑战连续几代的埋葬甲虫种群，看看它们如何反应以及它们使用什么样的耐药性管理策略。我们预测，埋葬甲虫通过管理不同的细菌如何通过它们产生的抗菌剂鸡尾酒的组成变化而相互竞争，从而降低细菌群落进化耐药性的速率。我们的研究结果有望为我们理解如何最有效地管理AMR提供重要的一步。

Antimicrobial resistance (AMR) is one of the most important public health issues that society currently faces. Inappropriate use of antibiotics has accelerated the rate at which bacteria have evolved resistance and the development of new antimicrobials is very expensive and time-consuming and has almost come to a halt. Consequently we need to develop better ways to sustainably utilize existing and future antimicrobials.However, there is a lack of consensus on the best way to manage resistance, especially for bacteria. Which resistance management strategy would be most effective? Is it most effective to reduce prescribing rates or should antimicrobials be given in combination, and if so, what combinations? It has been difficult to address these questions in a clinical setting and relevant experimental systems to validate resistance management strategies outside of clinical trials are currently rare. Here we proposal a novel approach to these problems: use organisms in which management of bacteria and other microbes is a fundamental part of their natural history to elucidate the most effective strategies to combat antimicrobial resistance. Burying beetles fit the bill perfectly. They process the carcasses of small vertebrates such as mice to rear their young and are unusual among invertebrates in having extended, complex parental care. In addition to feeding their offspring like birds do (burying beetle larvae beg to be fed and parents respond by regurgitating food - dead mouse) they also produce antimicrobial secretions to combat competition from microbes, especially bacteria. It is this latter form of parental care that we are most interested in here. Since there is evidence that burying beetles have been providing care and managing competition from microbes for approximately 100 million years there are likely to be substantial rewards from exploring what resistance management strategies they use.The particular novelty of our approach is to use experimental evolution to see how both beetles and bacteria respond to increased selection pressure from each other. We can therefore observe evolution in action and test the relative efficiency of different resistance management strategies directly. In particular we will challenge populations of burying beetles over successive generations with resistant bacteria that we will produce in the lab and see how they respond and what resistance management strategies they use. We predict that burying beetles reduce the rate at which bacterial communities evolve resistance by managing how different bacteria compete with one another through variation in the composition of the cocktail of antimicrobials that they produce. Our results are expected to provide a significant step forward in our understanding of how to manage AMR most effectively.