NIH National Institute of Allergy and Infectious Diseases, Creative Commons
Learning about human infections from studies of animal disease transmission
11 Jul 2017
This case study forms part of our Investing for Impact report, looking at how MRC- funded research delivers impact. More can be found in the Investing for Impact section of our website.
MRC-funded research into how antibiotic resistance can jump from farm animals to humans in 2015 highlighted potential new transmission routes to infections. This work has led to a new approach to re-sensitising resistant bacteria to existing antibiotics as well as new diagnostic technology.
Antibiotics are widely used in industries such as agriculture and farming, often as a “growth promoter” – micro-doses of antibiotics given to livestock will boost the animals’ weight, and thus get them to market faster. Unfortunately, these micro-doses can provide the perfect conditions for antibiotic resistance to evolve. This is because low doses of antibiotic are not lethal enough to kill bacteria, giving them opportunity to mutate and evolve mechanisms of antibiotic resistance. The ability of these resistant bacteria to then eventually jump from animals to humans is therefore of grave concern.
This concern was brought home in 2015 when researchers funded primarily by the MRC bought and analysed pre-packaged fresh meat products, labelled as being of UK farm origin, from supermarkets in five locations across England. Led by Dr Mark Holmes at the University of Cambridge, the study showed that a type of bacteria known as methicillin-resistant Staphylococcus aureus (MRSA) was isolated from this meat. It was the first time this particular strain of MRSA was identified in retail meat products in the UK. Its presence in the human food chain demonstrates yet another potential pathway for the transmission of antibiotic resistance from livestock to the broader human population.
Dr Holmes has experience in studying MRSA strains in animals and how these infections can cross over to cause disease in humans. In 2011, he and his team identified a novel strain of MRSA isolated from milk in British dairy cows. Resistance to methicillin is usually determined by testing the bacteria for the presence of a gene called mecA. However this new strain of MRSA was undetectable by this method; instead of mecA, these bacteria had a related gene subsequently named mecC. Worryingly, this new strain of MRSA was found in clinical samples from humans as well. Because these bacteria had mecC instead of mecA, it had the potential to be misdiagnosed when testing for MRSA. In 2012, in collaboration with the Health Protection Agency, Dr Holmes and his team helped design and implement a new diagnostic test that would be capable of detecting this mecC strain of MRSA, allowing scientists to identify the source and transmission of infection.
But could the difference between these two strains of MRSA be exploited to treat these infections? An innovative solution to the problem of antibiotic resistance is to attempt to re-sensitise resistant bacteria to existing antibiotics by exploiting our knowledge of the mechanisms behind resistance. For example, by using novel inhibitors or combinations of antibiotics that act synergistically, it could be possible to overcome antibiotic resistance. In 2014, Dr Holmes and his team published their results investigating this approach in the mecC strain of MRSA. When bacteria develop resistance to antibiotics like methicillin, they do so by producing an enzyme called β-lactamase which breaks down the antibiotic molecule, thereby making it harmless to them. Using a drug that can inhibit this enzyme (i.e. a β-lactamase inhibitor) with the antibiotic can render a previously resistant strain of bacteria once again sensitive to that antibiotic. Dr Holmes and his team demonstrated that the MRSA mecC strain was indeed susceptible to the combination of penicillin and the β-lactam inhibitor clavulanic acid.
This important work demonstrates that antibiotic resistance is a problem growing far beyond just humans, and has an impact on a multitude of industries. To tackle this, we need to closely monitor the transmission of antibiotic resistant bacteria between animals and humans as well as understand the mechanisms behind the process. We also need to transform agricultural practices to reduce the frequency of such events, working closely with veterinarians, farmers, and clinicians.
Award details: G1001787
Image description: Scanning electron micrograph of methicillin-resistant Staphylococcus aureus and a dead human immune cell