Acquisition and Selection of Antibiotic Resistance in Companion and Farmed Animals and Implications for Transmission to Humans

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Without antimicrobial drugs, the risk of bacterial infection would render many common medical procedures too dangerous to contemplate because of the risk of infections caused by "opportunistic bacteria". They can live on the patient's skin, or in their intestines, and infection occurs when bacteria get into parts of the body that are normally sterile. A perfect example is urinary tract infection (UTI) caused by faecal bacteria. E. coli is particularly abundant in human faeces so is perfectly placed to cause opportunistic infections. It is one of the most common causes of healthcare pneumonia, surgical site infection, bloodstream infection and UTI in the UK. In order to prevent against and treat opportunistic infections, patients are given antimicrobials.Almost all antimicrobials are "antibiotics", which means they are derived from natural chemicals produced by microbes found in the environment. Natural antibiotics have been present in the environment for millions of years, and so bacteria living in their presence have had time to evolve mechanisms that can resist their actions, encoded by "resistance genes". Opportunistic bacteria like E. coli can randomly acquire these pre-evolved resistance genes and in a single step, they become insusceptible to a particular antimicrobial. If that insusceptible E. coli colonises a person and then causes an opportunistic infection, the infection will not be treatable with that particular antimicrobial. We refer to this as "antimicrobial resistance" (AMR); however AMR bacteria don't just resist clinical antimicrobial therapy, they beat it.Animals also carry an abundance of E. coli in their intestines and are frequently treated with antimicrobials. This can select for the acquisition of AMR E. coli which can then be passed on to another animals, directly, or via contamination of the environment with faeces. Theoretically, the AMR E. coli could also be passed on to people, and there is much debate about whether such "zoonotic transmission" happens to any significant degree. This is an important debate because it has led to calls from some to dramatically reduce the amount of antimicrobials that are given to animals with the view that it will reduce the level of AMR in animals, and so the possibility of zoonotic transmission to people. But the potential impact on welfare and food production means this should only be done if there is evidence that it will work.In this project we will identify what drives acquisition of AMR in animals using E. coli as the exemplar bacterium and dairy cows and dogs as exemplar farmed and companion animals. We will test whether AMR bacteria encountered by an animal as it interacts with the environment influence the AMR profile in its faeces, and/or whether early life antimicrobial use plays a part in selection of AMR bacteria in animals. We will also test whether reducing antimicrobial use in dairy cows actually does reduce AMR in the near-farm environment that is contaminated with their faeces. We will test whether exercising in these contaminated near-farm environments influences the abundance of AMR bacteria in dogs, and whether there is any evidence of direct acquisition of AMR E. coli by dogs from near-farm environments, which might be brought into the home.Finally, we will investigate whether AMR abundance in human UTI E. coli reduces as antimicrobial drug prescribing reduces in primary care; whether living close to a farm affects AMR abundance in UTI E. coli; whether there is direct evidence for E. coli carried by dogs or found in near-farm environments contaminated by cattle faeces also causing UTIs in humans.These interlaced studies will provide much needed data about the management changes that might reduce AMR in animals and in humans, and are designed to address the fundamental question of whether zoonotic transmission is particularly significant as a driver of AMR in people relative to antimicrobial drug use by doctors.