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

抗生素耐药性(AMR)是当前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抗药性的速度，新抗菌剂的开发非常昂贵和耗时，而且几乎停滞不前。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。然而，对于管理耐药性的最佳方法，特别是细菌的耐药性，缺乏共识。哪种阻力管理策略最有效？降低处方率是最有效的，还是应该联合服用抗菌药？如果是，是什么组合？在临床环境中解决这些问题一直是困难的，而在临床试验之外验证耐药性管理策略的相关实验系统目前很少。在这里，我们提出了一种解决这些问题的新方法：使用细菌和其他微生物的管理是其自然历史的基本部分的生物体来阐明对抗抗菌素耐药性的最有效策略。埋葬甲虫完全符合这一要求。它们对老鼠等小型脊椎动物的身体进行处理，以饲养它们的幼崽，在无脊椎动物中，它们不同寻常的是拥有延长的、复杂的父母照料。除了像鸟类一样喂养后代(埋葬甲虫幼虫乞求喂食，父母通过反胃食物死亡的老鼠来回应)，它们还会产生抗微生物分泌物来对抗微生物，特别是细菌的竞争。在这里，我们最感兴趣的是后一种形式的父母照顾。由于有证据表明，埋葬甲虫在大约1亿年的时间里一直在提供护理和管理来自微生物的竞争，因此探索它们使用什么抗性管理策略可能会获得丰厚的回报。我们方法的特别新奇之处在于，利用实验进化来观察甲虫和细菌如何应对来自彼此的选择压力增加。因此，我们可以在行动中观察进化，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生产的抗药性细菌来挑战埋葬甲虫的后代，看看它们如何反应，以及它们使用了什么抗药性管理策略。我们预测，埋葬甲虫通过管理不同细菌如何通过它们产生的抗菌剂鸡尾酒的组成变化来管理不同细菌之间的竞争，从而降低细菌群落进化耐药性的速度。预计我们的结果将使我们在理解如何最有效地管理AMR方面向前迈进一大步。

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.