Antimicrobial resistance and how diagnostics research can help

It’s World Antimicrobial Resistance Awareness Week (18 – 24 Nov). We caught up with Prof Till Bachmann, IRR Group Leader and Co-Lead of the CIR Translational Medicine theme, to tell us about his research and how he’s tackling antimicrobial resistance.

What is antimicrobial resistance (AMR)?

Antimicrobial resistance is when the drugs which we use to treat infections by microorganisms, such as bacteria, viruses, fungi or parasites, don't work anymore.

How does resistance happen?

Let’s look at bacteria as one example. There are five most common ways of how antimicrobial resistance happens. 

The antibiotic needs to get into the bacteria, so the bacteria can physically prevent that from happening by having a thick and tight cell wall. Secondly, if the antibiotic does get in, the bacteria can pump it back out very quickly, which they are very effective in doing. Another way is if the antibiotic comes in and binds to its target, the bacteria can cut it up and inactivate the antibiotic. 

The bacteria can also alter its target so the antibiotic can’t bind anymore, again, making it inactive. Finally, what bacteria can also do, and this is really clever, is they can either make more of the antibiotic target or make a lot of variations of it. Therefore, the antibiotic can only bind to some targets, allowing the others to escape.

How do bacteria know how to do these resistance mechanisms?

The instructions on how to do these resistance mechanisms are stored in the genes – or instructional code - of the bacteria. It's very interesting because this code can change spontaneously, making the bacteria resistant. This is evolution – the bacteria evolve and its survival of the fittest.

The bacteria can also pass on that resistance information to other bacteria. So, the bacteria which have not been resistant before all of a sudden become resistant because they were told how to be. This is how resistance quickly spreads.

Why is it a problem?

Antimicrobial resistance leads to infections that are harder to treat, causing more severe illness and, in many cases, death. As resistant infections increase, we’re seeing a global rise in mortality linked to antimicrobial resistance.

Antimicrobial resistance leads to infections that are harder to treat, causing more severe illness and, in many cases, death.

Why has there been an increase in AMR?

We use too many antibiotics, and we use them in all aspects of our lives - in human healthcare, animal farming, plant agriculture, and they end up in the environment. This broad use creates many opportunities for bacteria to develop resistance. 

Resistant bacteria also move between these different areas, spreading the problem across all domains. Because all these settings are connected, we need to consider AMR in a One Health context including human, animal, plant and environmental health.

We need to consider AMR in a One Health context including human, animal, plant and environmental health.

How can we prevent AMR?

We should use less antibiotics and only when we really need them. To do that, we need to know what is wrong for example with a patient who is presenting with infection symptoms, if they need an antibiotic and if so, which antibiotic should be used.

How does your research address AMR?

Our research focuses on diagnostics. As Alain Mérieux, President of the Mérieux Foundation, famously said, ‘Without diagnostics, medicine is blind.’ In this case, diagnostics can provide information on whether a patient needs antibiotic treatment and if so, which ones to choose. 

AMR is driven by a web of factors - microbes, clinicians, patients, the public, and the environment all play a role. We still don’t fully understand all the cause-and-effect pathways. Because of that, we must approach it holistically rather than treating it as just a microbiological issue.

Where do you see the biggest opportunities for reducing infections?

Prevention is always best. Vaccines are powerful, but many infections - for example those caused by bacteria already normally living in our bodies - are difficult to target with vaccines. Handwashing is a powerful infection prevention measure. When infections do occur, rapid and accurate diagnostics are crucial to guide whether an antibiotic is needed and if it is, which one to prescribe.

…rapid and accurate diagnostics are crucial to guide whether an antibiotic is needed and if it is, which one to prescribe.

What diagnostics are you developing?

We work on molecular diagnostics for pathogen identification and AMR gene detection. Importantly, we avoid PCR amplification - a lab technique that makes many copies of a specific DNA segment - to keep things simple and fast. 

Instead, we use electrochemical biosensors (like blood glucose strips) to directly detect bacterial genetic information. These biosensors can be built into small devices that can detect genetic material from bacteria in samples like urine or blood. 

Which types of infections are you targeting?

Our core focus is bacterial infections, such as those in the urinary tract, respiratory tract, blood stream or wound infections. These are conditions where point-of-care tests, potentially even home-based tests, would make a significant impact. With these tests we detect bacteria, determine their species as well as their antibiotic resistance genes and eventually their antibiotic sensitivity.

Can you tell us about your work detecting host responses?

Beyond identifying pathogens and resistance genes, we measure the body’s response to infection through body biomarkers like proteins, microRNAs, and extracellular vesicles. 

Beyond infection, these can reveal for example, inflammation, liver injury and kidney injury in the body, which helps clinicians understand what’s happening in a patient. I feel I’m ideally placed to research this area, being in the Centre for Inflammation Research.

…these can reveal for example, inflammation, liver injury and kidney injury in the body, which helps clinicians understand what’s happening in a patient.

What role does the use of AI play for your diagnostics research?

We analyse how bacteria respond to antibiotics - changes in shape or behaviour - using microscopy and computer vision. This works somewhat like facial recognition for microbes. This approach could drastically speed up antibiotic susceptibility testing, which traditionally depends on waiting for bacteria to grow.

How important is collaboration with hospitals and clinicians?

It’s essential. We work closely with clinical microbiologists at the Royal Infirmary and clinicians in the Edinburgh Medical School to understand unmet needs and to access real clinical samples. These collaborations ensure our research remains grounded in actual patient care.

You’ve led major initiatives on diagnostic adoption. What challenges do innovators face?

Too often, technologies are pushed from the lab towards the clinic and then, adoption is slow if the tests don’t align with what clinicians and patients actually need. 

My work with and funded by organisations like JPIAMR (Joint Programming Initiative on Antimicrobial Resistance), Innovative Medicines Initiative and the World Health Organisation has focused on identifying barriers for development, adoption and use of diagnostics. 

My work…has focused on identifying barriers for development, adoption and use of diagnostics.

One key output was the development of target product profiles for AMR diagnostics. These profiles are clear specifications for what an effective diagnostic must deliver in the real world.

That thinking led to the DOSA project. What is it?

DOSA stands for Diagnostics for One Health and User Driven Solutions for AMR. Since 2018, I am coordinating this initiative which works with end users, people with lived experience of AMR and multiple partners in the UK and India with a broad range of expertise and backgrounds to develop diagnostic solutions for AMR. 

For human healthcare, DOSA brought together primary and community healthcare staff, patients, healthcare authorities and the project partners to co-design a simple, but powerful, paper-based diagnostics for urinary tract infections. Instead of concentrating only on the technology, we involved the people who will be using it from the start. For example, we asked what their pain points and needs were, and how they would use it. It’s about creating point-of-care diagnostics that are useful and therefore more likely to be adopted and used consistently.

It’s about creating point-of-care diagnostics that are useful and therefore more likely to be adopted and used consistently.

Three women using the UTI diagnostic strip test

How does this approach fit into the broader AMR response in Edinburgh?

AMR requires transdisciplinary collaboration - linking human, animal, plant, and environmental perspectives. Through initiatives I coordinate in Edinburgh, like the Edinburgh AMR Forum as part of Edinburgh Infectious Diseases and the new AMR Futures Lab at Edinburgh Futures Institute, we’re building transdisciplinary networks and initiatives that focus on sustainable impact beyond academic publications. 

…we’re building transdisciplinary networks and initiatives that focus on sustainable impact beyond academic publications.

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