The Importance of Eradicating Biofilms in the Fight Against Antimicrobial Resistance (AMR)

Biofilms, complex communities of microorganisms embedded in a protective extracellular matrix, present significant challenges in various sectors, including oral care, wound care, hospitals, food production, and the oil and gas industry. The organisms within the biofilm can be up to 1000 times more resistant to traditional antimicrobial treatments that target planktonic organisms leading to an increased risk of antimicrobial resistance (AMR). The fight against AMR continues to become increasingly important globally, with some projections estimating that if current trends continue, AMR could take the lives of 444 million people by 2050, and cost the global economy close to ￡100 trillion.

Controlling and eradicating biofilm necessitates the use of novel technologies and high concentrations of antimicrobial agents, and due to the regulatory landscape being slow to catch up, these technologies often go untested and their efficacy against biofilm can be unknown and unpredictable. Additionally, the impact of these treatments in promoting resistance in other species is not well studied and will require monitoring and continuous research development.

This article will look at some of the key areas that are negatively impacted by unwanted biofilms and the research and technologies that will require specific focus when combatting them.

Oral Care

In oral health, biofilms are primarily responsible for dental plaque formation, and if left unchecked can lead to tooth decay and gum diseases like gingivitis and periodontitis. The persistent nature of biofilms in the oral cavity can make them resistant to standard oral hygiene practices and treatments. This resistance can result in more frequent dental visits and the need for advanced interventions increasing healthcare costs significantly. Moreover, the improper use of antibiotics to treat oral infections can contribute to AMR, posing a broader public health risk.

Oral biofilm research focusses predominantly on development of gentle therapies that consumers can incorporate into their oral care routines which seek to control the formation of plaque and remove established plaque without damaging oral tissue. In practice, this could look like targeted antibiofilm agents which are introduced into toothpastes, mouthwashes, and dental materials, or oral probiotics which can outcompete biofilm-forming bacteria in the oral cavity.

To demonstrate efficacy of these treatments, antibiofilm agents are tested initially against single species biofilms produced by orally relevant organisms to establish basic efficacy. Further studies are then undertaken using multi-species and interkingdom biofilms, both newly established and mature, to gain a more complete understanding of treatment efficacy under complex conditions. More complex studies can be undertaken using gingival tissue to demonstrate the inflammatory response from biofilms and changes upon treatment.

Wounds and Hospitals

In hospital settings, biofilms on medical devices, wounds, and surfaces can lead to severe and life-threatening infections. For example, chronic wounds like diabetic ulcers often harbour biofilms, which complicate healing and lead to prolonged and expensive treatments. The presence of biofilms in hospitals can also facilitate the spread of nosocomial infections, which are notoriously difficult to treat due to the microorganisms' resistance to disinfectants and antibiotics, and these can and have caused the deaths of patients in healthcare settings. The financial burden includes extended hospital stays, additional medical treatments, and increased use of expensive antimicrobial agents, contributing to healthcare costs and resource allocation issues.

Research in this area focusses on developing technology to prevent biofilms forming on the surfaces of medical devices coupled with safe treatment of established and potentially chronic biofilm infection. Materials and coatings for medical devices may be produced with antibiofilm properties, including those containing silver nanoparticles, antimicrobial peptides, or antibiofilm agents which are released gradually from the surface. Similarly, wound dressings can be imbued with compounds that disrupt and prevent biofilm formation during wound healing. Bacteriophage therapy is a growing area of research in chronic wounds and infections that uses safe, non-pathogenic viruses which only target specific biofilm-forming bacteria and allow the body’s immune system to overcome the infection . Similar to oral biofilm research, the efficacy of antimicrobial agents on wound biofilms starts in single species biofilms of medically relevant organisms and can progress to assessing treatments against complex multispecies 3D models. Artificial wounds can be created in the laboratory to mimic the response to treatment. This testing therefore helps to indicate treatment success of new treatment candidates without the need for invasive animal studies.

Food Production

In the food industry, biofilms on processing equipment can harbour pathogenic bacteria, posing a risk of foodborne illnesses. These biofilms can withstand standard cleaning and sanitisation processes, leading to potential contamination of food products. The economic implications are profound, including product recalls, loss of consumer trust, and significant financial losses, as well as the obvious health risks to consumers on a global scale. Moreover, the misuse of biocides in trying to control these biofilms can contribute to the development of resistant strains, further complicating food safety management.

For food manufacturers, key areas of research are in antimicrobial surfaces which prevent the formation of biofilms, but also the development of natural anti-biofilm agents which are seen as safer and more acceptable to consumers. Of particular interest are compounds derived from plants, essential oils, and bacteriophages which can be screened against microorganisms and biofilms containing food-relevant strains. Additionally, the development of enzyme-based cleaners that breakdown biofilm matrices, combined with

improving the efficacy and safety of biocides used in disinfection processes, ensures that biofilms can be removed and killed as effectively as possible.

Energy Sector, and Oil and Gas

Biofilms in the oil and gas sector can cause severe issues like microbiologically influenced corrosion (MIC), which leads to the degradation of pipelines and equipment. This corrosion can result in costly repairs, downtime, and even environmental disasters due to leaks and spills. The financial implications include not only the direct costs of repair and replacement but also the potential environmental fines and remediation expenses. Furthermore, the challenge of biofilm-related corrosion is exacerbated by the microorganisms' resistance to biocides, pushing the industry to explore more potent and often more toxic chemicals, which can further contribute to environmental and AMR concerns. Biofilms can also be problematic in the renewable energy sector, with biofilm colonisation on solar panels, marine current exchange turbines, wind farms, and heat exchangers, reducing the efficiency of electricity generation.

Across the energy sector, research into ways to limit the impact of biofilms can cover three main areas – improved biofilm detection and monitoring, enhanced removal with improved biocides, and novel treatments to inhibit MIC. Detection of biofilms in this area can be performed using a variety of physical and biochemical techniques. Laboratory studies into molecular detection using microbial DNA and Fluorescence in situ Hybridisation (FISH), as well as the development of new biosensors, can highlight specific biofilm-forming organisms present in natural and engineered environments. Enhanced biofilm removal can be investigated by testing biocide formulations against simple and complex biofilm models in static, spun, or flow reactors to mimic the different conditions under which the biofilms will grow and be treated. To control corrosion, potential MIC compounds can be screened for material compatibility, as well as efficacy against specific microorganisms such as sulfate-reducing bacteria (SRB), iron-oxidising bacteria (IOB), and acid-producing bacteria (APB).

Conclusion

The eradication of biofilms across these sectors is not merely a matter of improving efficiency and reducing costs; it is crucial for public health and safety. Addressing biofilms effectively requires a multidisciplinary approach, including advances in cleaning technologies, better antimicrobial stewardship, and the development of novel treatment strategies that can penetrate biofilms and target resistant microorganisms. Such measures are essential to curbing the spread of AMR and ensuring the long-term sustainability of healthcare, food safety, and industrial operations.

BluTest Laboratories — A Tentamus Company are delighted to be attending and presenting at the annual AMR congress 2024 in Philadelphia, USA. This event represents an opportunity for the wider communities of science, government, and industry to share ideas and combat the pressing issue of AMR.

Tracy Rivett (Young), PhD. and Daniel Yaxley will be sharing their insight into the effects of biofilms on AMR and the challenges faced in efficacy testing.

The article is written by General Manager at BluTest Laboratories — A Tentamus Company , Daniel Yaxley .