REHAB: The Environmental Resistome

REHAB

The environmental REsistome: confluence of Human and Animal Biota in antibiotic resistance spread (REHAB)

OVERALL STUDY AIM

We do not fully understand how important types (species) of bacteria and packages of genetic material (genes) coding for antibiotic resistance move between humans, animals and the environment, or where, how and why antibiotic resistance emerges. This study aims to look in detail on a genetic level at bacteria in farm animals, human/animal sewage, sewage treatment works and rivers, to work out the complex network of transmission of important antibiotic-resistant bacteria and antibiotic resistance genes. We will use this information to work out how best to slow down the spread of antibiotic resistance between humans, livestock and the environment.

STUDY BACKGROUND AND AIMS IN MORE DETAIL

Infections are one of the most common challenges in human and animal medicine, and are caused by a range of different micro-organisms, including viruses and bacteria. Amongst bacteria, there are some species, or types, of bacteria, which can live harmlessly in human and animal intestines, sewage, and rivers, but can also cause disease in humans and animals if they get into the wrong body space, such as the bloodstream or urine. Examples of these bacteria include E. coli, and other similar organisms, which belong to a family of bacteria called “Enterobacteriaceae”.

It has generally been possible to treat infections caused by bacteria using several classes of medicines, known as antibiotics. Different antibiotics kill bacteria in different ways: for example, they can switch off critical chemical processes that the bacteria need to survive, or they can break down the outer shell of the bacteria. In response to the widespread use of antibiotics, bacteria have changed over time, finding ways to alter their structure so that antibiotics no longer have a target to act on, or by producing substances that break down the antibiotic before it has a chance to act i.e. they develop antibiotic resistance. This adaptation is caused by changes in the bacterial genetic code. Bacteria can also rapidly acquire “packages” of antibiotic resistance genes from other surrounding bacteria. This is known as horizontal gene transfer. Through these mechanisms, members of the Enterobacteriaceae family of bacteria have developed antibiotic resistance to a number of different antibiotics over a short period of time. In some cases we are no longer able to treat these infections with the antibiotics we have available.

Studying antibiotic resistance and horizontal gene transfer in bacteria found in humans, animals and the environment is difficult because we cannot directly see how bacteria change their genetic code and acquire parcels of resistance genes through horizontal gene transfer in the environment. However, new “Next Generation Sequencing” (NGS) technologies allow scientists to look in great detail at the genetic code of large numbers of bacteria. Comparing this information for bacterial species which have been living in different parts of the environment (e.g. human/animal sewage, sewage treatment works, rivers) allows us to see how bacteria have evolved to become resistant to antibiotics, and how resistance genes have been shared between them.

This study will use NGS technologies to look at the genetic code of large numbers of Enterobacteriaceae bacteria found in humans, animals (pigs, sheep and poultry), sewage (pre-, during and post-treatment), and rivers. These different groups/areas will be sampled in different seasons over a year to determine how antibiotic resistance genes move around between these locations and over time, and what factors might influence this movement. We will also be investigating whether various chemicals and nutrients in the water may be affecting how quickly horizontal gene transfer occurs. Understanding this is essential to work out how we might intervene more effectively to slow the spread of antibiotic resistance genes and bacteria, and keep our antibiotic medicines useful.