Spotlight on: Antimicrobial resistance – meeting the challenge of resistant bacteria

What is antimicrobial resistance?

Antimicrobial resistance (AMR) occurs when microbes – bacteria, viruses, fungi and parasites – develop a defence against the drugs which are designed to kill them. Research is needed into resistance among all microbes, but the biggest current global threat is from drug-resistant bacteria. With the majority of the world’s bacteria having developed some level of resistance to antibiotics, we are now at the stage where we are using our last resort drugs. It is clear that new treatments and strategies to tackle AMR are urgently needed.

The rise of resistant bacteria

The discovery of antibiotics is considered one of the greatest medical achievements of the 20th century. Since Sir Alexander Fleming discovered penicillin in 1928, antibiotics have been used to save the lives of millions. From treating minor cuts and grazes to their use in major operations and serious diseases, these drugs have drastically improved our quality of life and increased our lifespan.

But antibiotics are rapidly becoming ineffective. Their overuse and misuse – in agriculture and human medicine – has led to a growing number of bacteria in humans, animals and the environment that are resistant to them. Certain strains of tuberculosis, methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile, no longer respond well to current antibiotics. Additionally we are seeing the worrying emergence of multidrug-resistant bacterial strains which have shown resistance to many, or even all, available antibiotics.

Antibiotics can treat bacterial infections, but they are ineffective against viruses or other types of infection. According to a WHO survey  in November 2015 almost two thirds of people wrongly believe antibiotics can be used to treat colds and flu. By taking them correctly, and using them when necessary, antibiotics are more likely to work when we need them. In some countries antibiotics are available without a prescription. Our livestock and pets are given antibiotics too and this exposure helps to drive bacterial resistance, for example estimates show that up to 80 per cent of all the antibiotics sold in the US are used in farm animals.

The problem of AMR is made worse by the fact that few new antibiotics have been developed over the last thirty years. This is because antibiotic development is scientifically very challenging: bacteria can develop resistance very quickly, rendering new drugs useless after a short period of time. Developing antibiotics is also less profitable than developing other drugs. As a result, most pharmaceutical companies have focused their attention elsewhere.

Fighting resistance through research

Antobiotic capsules (click to read more about our groundbreaking work)

Tackling the problem of AMR will depend heavily on interdisciplinary research. First, it will be crucial to understand the many factors that lead to resistance around the globe. This includes environmental factors such as the use of antibiotics in agriculture and fish farming and human behaviours like antibiotic overprescribing and hygiene practices. In order to reduce and control AMR, it will be essential to address these behaviours; for example, by changing how farmers and vets produce livestock for human consumption, and changing attitudes towards infection, prescribing, and the use of antibiotics among the public and healthcare professionals in the UK and abroad.

We also urgently need to develop new drugs and treatments to combat the rise of resistant bacteria. For instance, identifying parts of resistant bacterial cells that could be used as new drug targets, will allow scientists to come up with ‘next generation’ antibiotics that can kill these cells quickly without harming the patient. The development of more specific, disease-tailored antibiotics will also help us to cut down on the number of drugs being used.

Professor David Holden

To develop new antibiotics, it is important to explore how certain bacteria survive and become resistant to these drugs. Professor David Holden is an MRC researcher at Imperial College London who is studying persister cells in salmonella. Unlike most other bacterial cells, persister cells do not replicate  meaning they can ‘lie low’ to escape antibiotic action. This makes them difficult for current antibiotics to track down and kill. David has shown for the first time how bacteria form persister cells immediately after they are attacked and consumed by the host’s immune system. This is in response to the acidic environment inside the immune cells. David’s findings may bring us closer to developing new antibiotic drugs that are effective against this type of bacterial cell.

Professor Simon Foster (click to read more)

Scientists are also exploring alternative therapies – such as vaccines – which could treat bacterial infections in the future. Professor Simon Foster, an MRC scientist from the University of Sheffield, is working on developing vaccines (PDF, 240KB) (PDF, 240KB) against Staphylococcus aureus (S. aureus) and MRSA infection. S. aureus is a bacterium that causes blood infections and wound abscesses. It is resistant to current antibiotics, and one particular strain, MRSA, is responsible for many hospital deaths each year. Simon has identified two promising protein targets that can be used to develop these vaccines, and is planning to test the new treatments in clinical trials over the next few years.

Another pioneering approach in AMR research is the development of ‘smart surfaces’. These are materials which are designed to prevent the build-up of harmful bacteria that can lead to infection, often by steadily releasing antibiotics. MRC scientists are currently working on a number of exciting projects in this area. They include a new surface for catheters to reduce infections, a special coating on joint implants that controls infections at the site of surgery, and an antibiotic implant to clear up recurrent ear infections. If successful, these smart surfaces have the potential to transform the way that we prevent and treat bacterial infections.

In the fight against AMR, we will also need to understand how our bodies respond to infection by resistant bacteria so we can find new ways of fighting such infections. By focusing on improving the way that we diagnose infections, we can make sure that patients are prescribed the most effective drugs and treatments.

A new generation of diagnostic tools are starting to come through the pipeline, providing creative solutions to try and reduce unnecessary prescribing of antibiotics. As part of a project led and managed by the MRC on behalf of the UKCRC Translation Infection Research Initiative, Professor Alison Holmes has come up with a tool to support healthcare professionals with antibiotic-prescribing decisions. The Imperial Antibiotic Prescribing Policy (IAPP) smartphone app helps professionals choose the most appropriate treatment to ensure antibiotics are prescribed appropriately. In its first three years, the app has been consulted more than 105,000 times.

Researchers at the University of Bath have developed a light-up dressing that indicates whether burns are infected or not. They recently received a £1m award from the MRC via the Biomedical Catalyst to test its effectiveness at detecting infection in wound swabs and blister fluid from patients. The award will also fund the development of prototype dressings to be tested on patients.

How is the MRC involved?

MRC activity in antimicrobial resistance

The MRC is addressing the key challenges in antimicrobial resistance (AMR) by undertaking cutting-edge research in collaboration with other research councils, and by drawing together a range of scientific expertise from the UK and abroad. Our scientists are taking unique approaches to AMR that will help to improve our understanding of resistance, and ultimately, our ability to develop new drugs and therapies. To learn more about the exciting scientific discoveries being made by MRC scientists in this area, read our blog post on attacking antibiotic resistance.

Working together to find solutions

Collaborative working will be crucial for tackling AMR. Ties between academia and industry will be important for helping scientists to identify treatments and diagnostics that are likely to make it to the clinic. It will also be essential for different scientists – such as chemists and biologists – to work together to find new classes of drugs, and to potentially revive old drugs with new science. As we work to address the scale of the AMR problem, we will need to involve experts from further scientific areas such as engineers, environmentalists, social scientists and economists.

To encourage a coordinated approach to tackling AMR, we have set up the Antimicrobial Resistance Funders’ Forum (AMRFF). AMRFF brings together research councils, health departments, governmental bodies and charities that either provide support for AMR research or have an interest in AMR. The Forum aims to provide a strategic overview of AMR research in the UK and to create a shared vision for the future of AMR research and its potential impact on policy and treatments. AMRFF will also strive to improve AMR research by identifying and addressing any research gaps, and coordinating and supporting research activity across different disciplines. In addition, it will work towards improving the understanding and profile of AMR research in the UK and abroad.

A national AMR programme

Drawing on the work of the AMRFF, in July 2014 the MRC began a major new AMR research initiative in partnership with all the UK research councils. This cross-council initiative will address the major challenges in AMR research by setting up four themed programmes. These will:

  • Understanding resistant bacteria
  • Accelerating therapeutic and diagnostics development
  • Understanding AMR and the real world interactions
  • Behaviour within and beyond the health care setting

So far the initiative has committed £36m to support 48 innovative, cutting-edge proposals under the four themes as part of its first phase. The aim of this phase is to attract different expertise into the area of AMR and support interdisciplinary teams to develop research programmes that address AMR in a holistic way.

Going global 

AMR is a global problem, which means that our work in this area extends beyond the UK. The MRC is a partner in the Newton Fund, a UK Government initiative to strengthen research and innovation partnerships between the UK and emerging knowledge economies to benefit global health, investing up to £150 million each year between 2015 and 2021, with partner countries providing matched resources within the Fund.  Since 2012 the MRC has been representing the UK on the EU Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), which is coordinating research across18 European countries, plus Canada, Israel Argentina, and Japan, to address AMR at a multinational level. As part of this work, the MRC led a mapping exercise to quantify the scale and scope of publicly funded antibacterial resistance research across JPIAMR countries and at the European Union (EU) level from 2007 to 2013. This has helped us to identify gaps and opportunities and will continue to be used to guide future AMR research. Watch this video on JPIAMR to learn more about the important work being done by this initiative. We are also broadening our efforts outside of Europe, working with colleagues in India and China to tackle AMR.