The effect of temperature on the ecology and evolution of antimicrobial resistance in microbial communities.

当细菌获得了不被我们设计用来杀死它们的药物伤害的能力时，抗生素耐药性就会发生。越来越多的感染--如肺炎、肺结核和淋病--由于抗生素耐药性细菌而变得越来越难治疗。最近对欧洲和美国抗生素耐药性水平的研究发现，较高的温度与较高的抗生素耐药性水平有关。这项工作提出了一个极其重要的问题：气候变暖会使抗生素耐药性问题恶化吗？这个问题的答案很可能在于一个叫做质粒转移的过程对温度的反应。质粒是遗传物质的短片段，可以从一种细菌传递到另一种细菌，并且是抗生素耐药性传播的关键途径之一。质粒的转移尤其重要，因为它允许细菌从社区中的其他细菌获得现有的抗生素耐药性，而不必自己开发新的耐药性途径。然而，我们不知道温度如何影响质粒转移。了解温度如何影响质粒转移速率以及质粒在细菌群落中的维持情况是我研究的关键目标。我特别感兴趣的是，加热对质粒转移的影响是如何由供体（质粒携带者）和受体（无质粒）细菌对温度的反应决定的。在没有抗生素的情况下，作为一个质粒载体可能是昂贵的，所以我将测试在不同温度下存在和不存在抗生素的情况下，耐药性的成本和收益如何变化。质粒转移可以在几秒钟内发生，但随着细菌适应新的温度并进化以克服携带质粒的成本，几天、几周或几年后，转移速率可能会发生变化。由于细菌生长最好的地方进化速度可能更快，温度对质粒转移和持久性的影响可能会随着时间的推移而改变。为了测试这些想法，我将使用一个由15种细菌组成的模型实验系统，我可以很容易地操纵它来探索质粒转移如何在短期和长期内随温度变化。我将联合收割机把这些实验与数学模型和DNA测序结合起来。为了了解我在简单实验中的发现如何在更自然的条件下发挥作用，我将跟踪质粒转移及其在自然群落中的维持。虽然我的工作是实验性的，但它距离农业应用只有一步之遥，抗生素通常用于牲畜和农作物的杀虫剂。这导致了更广泛的环境-土壤，河流和农田等地方-作为抗生素耐药性的水库，可以转移到潜在的有害细菌。农场监测可以跟踪抗生素耐药性水平的季节性变化。在这种情况下，我的研究将提供线索，为什么阻力水平可能在一年中的不同时间有所不同。此外，我的研究可以告诉农民在什么温度下使用抗生素可以最好地限制耐药基因在环境中的传播和持久性。除了这些重要的应用，我的研究还将为温度如何影响生态和抗生素耐药性的进化提供基本见解，从单个细菌物种到整个微生物群落。这将为生态学研究人员提供重要的一般见解，因为越来越清楚的是，多种压力源（例如变暖和抗生素压力）的相互作用可能与孤立的压力源非常不同。最重要的是，我的研究可以帮助我们预测气候变化是否会加剧环境中的抗生素耐药性问题。

Antibiotic resistance occurs when bacteria acquire the ability to not be harmed by the drugs we have designed to kill them. A growing number of infections - such as pneumonia, tuberculosis, and gonorrhoea - are becoming harder to treat as a result of antibiotic resistant bacteria. Recent studies looking at levels of antibiotic resistance across Europe and the US found that higher temperatures are associated with higher levels of antibiotic resistance. This work raises an extremely important question: will climate warming make the problem of antibiotic resistance worse?The answer to this question may well lie in how a process called plasmid transfer responds to temperature. Plasmids are short sections of genetic material that can be passed from one bacterium to another, and are one of the key ways through which antibiotic resistance can spread. The transfer of plasmids is especially important because it allows bacteria to obtain existing antibiotic resistance from other bacteria in the community rather than having to develop new resistance pathways themselves. However, we do not know how plasmid transfer is impacted by temperature.Understanding how temperature impacts the rate of plasmid transfer and how well plasmids are maintained in bacterial communities is the key objective of my research. I am particularly interested in how the effect of warming on plasmid transfer is determined by the response of both the donor (plasmid-carriers) and recipient (plasmid-free) bacteria to temperature. Being a plasmid-carrier can be costly in the absence of antibiotics, so I will test how the costs and benefits of having resistance change in the presence and absence of antibiotics at different temperatures. Plasmid transfer can occur in a matter of seconds, but over days, weeks, or years the rate of transfer may change as bacteria adapt to novel temperatures and evolve to overcome the costs of carrying the plasmid. As rates of evolution are likely to be faster where bacteria grow best, the effects of temperature on plasmid transfer and persistence could change over time. To test these ideas, I will use a model experimental system consisting of 15 bacterial species that I can easily manipulate to explore how plasmid transfer changes with temperature over the short- and long-term. I will combine these experiments with mathematical modelling and DNA sequencing. To see how my findings in simple experiments play out under more natural conditions, I will track plasmid transfer and their maintenance in natural communities. Although my work is experimental, it is only one step away from applications in agriculture, where antibiotics are routinely applied to livestock and as pesticides on crops. This has resulted in the wider environment - places such as soils, rivers, and farmland - acting as a reservoir for antibiotic resistance that can transfer into potentially harmful bacteria. Farm surveillance can track seasonal changes in levels of antibiotic resistance. In this context, my research will provide clues as to why levels of resistance may be different at different times of the year. Moreover, my research could inform farmers at what temperatures the application of antibiotics may work best to limit the spread and persistence of resistance genes in the environment.Away from these important applications, my research will provide fundamental insights into how temperature impacts the ecology and evolution of antibiotic resistance, from individual bacterial species to entire microbial communities. This will provide general insights that are important for ecology researchers, as it is becoming increasingly clear that the interaction of multiple stressors (e.g. warming and antibiotic stress) can be very different to either stressor in isolation. Most importantly however, my research can help us predict whether climate change will exacerbate the problem of antibiotic resistance in the environment.