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

Lead Research Organisation: UNIVERSITY OF EXETER
Department Name: Biosciences

Abstract

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.
 
Title rTPC 
Description rTPC is an R package that helps fit thermal performance curves (TPCs) in R. rTPC contains 24 model formulations previously used to fit TPCs and has helper functions to help set sensible start parameters, upper and lower parameter limits and estimate parameters useful in downstream analyses, such as cardinal temperatures, maximum rate and optimum temperature. 
Type Of Material Computer model/algorithm 
Year Produced 2023 
Provided To Others? Yes  
Impact It has been downloaded over 1000 times, used by researchers in over 80 countries. 
URL https://padpadpadpad.github.io/rTPC/