Bacteria are becoming less responsive to antibiotics: technological innovation is crucial
Christel Kuik and Prof. Dr. Chris Arts are involved in research within the national NWA DARTBAC1 consortium. This collaborative initiative aims to investigate the increasing phenomenon of bacteria becoming unresponsive to antibiotics. As this issue grows, the number of infections—across all diseases and worldwide —is expected to rise significantly in the coming years, posing a major challenge to the medical field. Raising awareness about this issue is one of DARTBAC's objectives. Another critical goal is developing new material technologies that can serve as alternative treatment methods. Christel Kuik is conducting PhD research on bacterial biofilm infections. Chris Arts, Professor of Translational Biomaterials, is the lead researcher for DARTBAC and also heads the consortium.
Raising awareness
Chris Arts: “When bacteria no longer respond to antibiotics, it means they have become resistant. Antibiotic resistance, or AMR, isn’t a significant problem in the Netherlands yet, but it will be. As bacteria become increasingly resistant to antibiotics, we will see more infections and more cases where we are unable to help patients with infections. It’s harsh to say, but when infections are uncontrollable, it can lead to either amputation—if we act in time—or the patient’s death. We’ll see more cases in the Netherlands where people simply die from pneumonia. This is something we haven’t experienced in the last 60 years.
Compared to the rest of Europe, the Netherlands is still doing relatively well, but resistance is rising quickly. I anticipate that in the future, this will be the biggest issue for medical science. Within 20 years, antibiotic resistance will become the leading cause of death worldwide. Yet, awareness about this issue is lacking. Preventing the entire problem is impossible. The best we can do is try to minimize its effects. That’s what our consortium’s research aims to contribute to.”
Orthopaedic surgeries
Christel Kuik: “Antibiotic-resistant bacteria affect all medical fields, including orthopaedics. Each year in the Netherlands, around 80,000 hip and knee replacement surgeries are performed. Resistant bacteria are a significant problem in these operations, as they can form a biofilm on implants. This biofilm is a complex, slimy layer of bacteria accumulated on surfaces. Once this layer is formed, the implant often needs to be removed, which is very burdensome for patients. Now that we know antibiotics are increasingly ineffective against infections, we are focusing on two alternative methods. The first is to gain more control over the development of biofilms. The second is to prevent bacteria from attaching to implant surfaces or killing them using material technologies.”
Understanding biofilm formation
Christel Kuik: “Biofilm formation is a natural survival strategy for bacteria. Producing this slimy layer is a simple and effective way for them to protect themselves. Unfortunately, they are incredibly successful at it. You can find biofilms in Arctic ice, Yellowstone geysers, and even Dutch ditches—and, as I mentioned, on medical implants. To study biofilm formation on implants, we need to visualize the adhesion process. A few years ago, this wasn’t possible, but now we can, thanks to ‘mass spectrometry imaging.’ This technology enables us to visualize molecules. We replicate implants by creating small titanium implant models. On these, we grow bacteria, which then form biofilms. Using mass spectrometry imaging, we gather information about biofilm behavior, observing the composition of the slimy layer and how bacteria communicate within it. We aim to pinpoint where bacterial communication triggers events like reproduction or migration to other body parts. To do this, we analyze different layers of the biofilm, including the surface of the implant and the surrounding body cells. This information helps us better understand bacterial communication.”
Innovative material technologies
Chris Arts: “By understanding how biofilms form and how bacteria communicate, we can figure out the best ways to disrupt this communication. This opens up new therapy options, such as preventing the biofilm from adhering to surfaces in the first place. That’s why we’re working on developing materials to kill or disrupt bacteria during the attachment process. For example, we’re developing materials like bioactive glass, which works differently from antibiotics. Bioactive glass changes certain values (like acidity) to halt bacterial growth while simultaneously destabilizing bacterial cell walls through mechanical effects. Another innovation is ‘induction heating,’ developed by Leiden University, a consortium partner. This involves heating implants to 70°C before insertion, allowing body cells to attach while making it harder for bacteria to adhere. We don’t yet know the exact mechanism, but we have confirmed it in several experiments. This could lead to a very simple and widely applicable method.
We are also collaborating with TU Delft on 3D printing implant surfaces to hinder bacterial adhesion and working on antimicrobial gels and coatings containing silver with bacteria-killing properties. Next to that we’re also working on certain gels with antimicrobial compounds (substances that can kill or slow the growth of microorganisms like bacteria), which can be applied to plates or prostheses to prevent attachment. All these methods share a common principle: using technology to prevent bacterial adhesion or locally kill bacteria. Approaching this problem from a material technology perspective is relatively new, as this field has traditionally focused on antibiotics. Fortunately, material science offers many alternative solutions. Of course, we also know that, instead of trying to cure it, preventing such bacteria from forming is the most effective approach."
Impact
Chris Arts: “Our research combines fundamental and translational science, with both aspects reinforcing each other. Bioactive glass is already being used in patients, and the first clinical trials for coatings and induction heating will begin in 2025. We are now looking in detail at how these material technologies work and why they work. This fundamental knowledge is crucial for conducting solid materials technology research."
Christel Kuik: “Studying bacterial infections is highly relevant to medicine. Tackling infections is crucial for addressing antibiotic resistance and improving patient outcomes. Our research uniquely combines expertise from orthopaedic surgeons, microbiologists, and chemical analysts. This multidisciplinary approach is vital for solving this problem. Usually, as scientists, we’re on our own islands and don’t know what each other can do. Now that we’re sharing knowledge and getting a bigger picture of the problem, it’s truly rewarding. It’s exactly what’s needed to hopefully solve this issue. We have so many material and imaging technologies now that allow us to investigate so much. That gives me hope for the future."
Chris Arts: “The societal impact of our work could be huge. A prosthesis costs a few thousand euros. That’s still manageable. But if we need to replace an infected prosthesis, and we run into complications, the costs can rise to 100,000 euros per patient. If we can avoid those costs, we prevent serious financial strain on society. Avoiding such costs not only saves money but also spares patients the burden of additional surgeries. When new techniques reach the clinic, it will be a blessing for patients who don’t need their prosthesis replaced.
The impact of our research, and our consortium, also lies in raising awareness. We know that the number of infections is going to rise dramatically due to increasing antibiotic resistance. It’s no longer science fiction; it’s already a reality. This will be a problem for all disease areas. Given the magnitude of the problem, it can only be addressed in a multidisciplinary way. That’s why I’m so enthusiastic about our consortium – and about consortia in general. You can just accomplish more together!"
1The NWA consortium (National Research Agenda) DARTBAC stands for Dutch Antimicrobial Resistance Technology Development and Biofilm Assessment Consortium. It involves various academic, medical, and industrial partners.
Photo: Joey Roberts
Text: Eline Dekker
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