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

当细菌获得不受我们设计的杀死它们的药物伤害的能力时，就会产生抗生素耐药性。越来越多的感染，如肺炎、肺结核和淋病，由于抗生素耐药细菌的存在，正变得越来越难以治疗。最近对欧洲和美国抗生素耐药性水平的研究发现，高温与更高水平的抗生素耐药性有关。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种被称为质粒转移的过程如何对温度做出反应。质粒是遗传物质的短片段，可以从一个细菌传递到另一个细菌，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那里获得现有的抗生素耐药性，而不必自己开发新的耐药途径。然而，我们不知道质粒转移如何受到温度的影响。了解温度如何影响质粒转移的速度以及质粒在细菌群落中的维持程度是我研究的关键目标。我特别感兴趣的是，变暖对质粒转移的影响是如何由供体（质粒载体）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，作为质粒载体的成本可能会很高，所以我将测试在不同温度下，抗生素存在和不存在时，抗性的成本和收益是如何变化的。质粒转移可以在几秒钟内发生，但在几天、几周或几年的时间里，随着细菌适应新的温度和进化以克服携带质粒的成本，转移的速度可能会发生变化。在细菌生长最好的地方，进化速度可能更快，因此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在短期和长期内是如何随温度变化的。我将把这些实验与数学建模和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，但它离农业应用只有一步之遥，在农业中，抗生素通常用于牲畜，作为杀虫剂用于作物。这导致了更广泛的环境——土壤、河流和农田等地方——成为抗生素耐药性的储存库，这些耐药性可以转移到潜在的有害细菌中。农场监测可以追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，为什么抗性水平在一年中的不同时间可能不同。此外，我的研究可以告诉农民，在什么温度下使用抗生素可能最有效地限制抗性基因在环境中的传播和持续存在。除了这些重要的应用之外，我的研究还将为从单个细菌物种到整个微生物群落，温度如何影响抗生素耐药性的生态和进化提供基本见解。这将为生态学研究人员提供重要的一般性见解，因为越来越清楚的是，多个压力源（例如变暖和抗生素压力）的相互作用可能与单独的任何一个压力源都大不相同。然而，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.