Antibiotic resistance of microorganisms is a serious threat to global health nowadays because it compromises our ability to control them. Even though it can occur naturally, inappropriate usage of antibiotics/antimicrobial compounds can accelerate it significantly. Therefore, simply treatable infections, such as pneumonia, become very hard to treat due to the ineffectiveness of antibiotics. According to recent studies, in 2019 antibiotic-resistant bacteria killed 1.2. million people and contributed to another 5 million deaths worldwide [1]. Such a phenomenon is usually caused by the development or acquisition of resistance mechanisms by microorganisms as their exposure to antimicrobial compounds creates a strong potential for evolution of resistance. 

In medicine, antimicrobial substances can be also used as coatings on biomedical surfaces such as catheters or implants. Once inserted into human bodies, such surfaces can be colonized  by bacteria forming hard-to-treat biofilms [2]. 

What are biofilms? 

Simply speaking, biofilms are aggregates of one or more types of microorganisms that can grow on many different surfaces [3]. These microorganisms become embedded within self-produced, extracellular matrix (composed of many different polymeric substances e.g. long-chained sugars) [2]. Bacterial biofilms have a lot to offer: social cooperation, easier resource capture and better survival following exposure to antimicrobial compounds which make them an attractive option for free-living bacterial cells [3]. 

To give you a better understanding of biofilms, a very common example of it is dental plaque – a sticky film of bacteria constantly forming on teeth. 

The major problem with biofilms is when they start forming on biomedical surfaces (as I mentioned earlier – catheters or implants) and become very hard-to-treat entities. It has been recognised that biofilm-associated infections are the majority of chronic bacterial infections [2]. Unfortunately, our knowledge regarding antimicrobial-resistant bacteria growing on biomedical surfaces is still quite limited at the moment which makes it an even harder issue to tackle [2]. 

BEAT-AMR Project

To detect any differences between the responses of resistant and non-resistant bacteria to antimicrobial-coated surfaces, a BEAT-AMR project has been set up. 

The BEAT-AMR Project – Antimicrobial Resistance in Biofilms – was a collaborative research project set up in 2017 which aimed to establish a fundamental understanding of the interplay between antimicrobial surface coatings, microbial biofilm formation, and antimicrobial resistance evolution within biofilms [2]. 

The way in which the project tried to establish such an understanding was to perform a series of laboratory studies on the common biofilm-forming pathogen Pseudomonas aeruginosa. Pseudomonas aeruginosa is a bacteria most commonly found in soil or water that can cause certain infections in humans like blood infections, infections in the lungs (pneumonia) or other parts of the body after surgery [4]. These infections are in general treated with antibiotics, although they are becoming more and more difficult to treat due to increasing antibiotic resistance, especially in patients exposed to nosocomial environments [4]. 

In the BEAT-AMR project, biofilms of Pseudomonas aeruginosa were grown on test surfaces and investigated with imaging technologies like atomic force microscopy and confocal laser scanning microscopy as well as modern sequencing technologies including metagenomics and metatranscriptomics. Specific hypotheses were tested in clinical settings at the final stages of the project to enable the formulation of clinical recommendations for the combined use of antimicrobial surfaces and antibiotics to minimize resistance spread and evolution [2]. 

Collaborative approach

BEAT-AMR project was a cooperation of four European partners: Bundesanstalt für Materialforschung und -prüfung ( BAM, Germany), Swiss Federal Laboratories for Materials Science and Technology (EMPA, Switzerland), University of Southampton (UK) and University Medical Center Groningen (The Netherlands). Michał Ciok, a PhD candidate at the University of Bayreuth, at that time a Master’s thesis student at BAM, took part in this project. 

The team from BAM aimed to identify antimicrobial-antibiotic combinations that would select for and against antibiotic resistance and to determine population dynamics of resistant strains in biofilms. 

Because of preventative and therapeutic approaches in clinical settings (application of multiple different antibiotics – coated on implanted biomedical surfaces and systemically  administrated), bacteria causing infections are exposed to different drugs during biofilm formation [5]. As a result, biofilms formed by resistant bacteria are harder to treat than biofilms formed by non-resistant bacteria. Interestingly, it has been shown that exposing non-resistant and resistant bacteria to the combinations of various toxic compounds can lead to the preferential survival of either one or another [5]. Thus, at first Michał Ciok and other scientists from the BAM identified antimicrobial-antibiotic combinations that potentiate their combined efficacy against microbes and the ones that suppress each other’s effects [6]. To establish the basis of how to choose the best combination of antibiotics during a treatment (to prevent infections with antibiotic-resistant bacteria), scientists exposed tested drug combinations to populations in which resistant and susceptible bacteria were mixed. Because of that, the team managed to select antimicrobial-antibiotic combinations that were selected either for or against antibiotic resistance [5]. Combinations that can select sensitive strains are preferred as they can inhibit the proliferation of resistant strains and slow down antibiotic resistance evolution.

It is worth noting that in the context of the Polish pharmaceutical market and the development of scientific research, issues related to bacterial resistance to antibiotics constitute an extremely significant problem.

References:

1. Murray CJ, Ikuta KS, Swetschinski L, Robles Aguilar G, Gray A, Han C, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. 2022 Feb 12;399(10325):629–55. Available from: https://dx.doi.org/10.1016/S0140-6736(21)02724-0
2. Bundesanstalt für Materialforschung und -prüfung (BAM). BEAT-AMR – Antimicrobial Resistance in Biofilms [Internet]. 2022. (www.bam.de). Available from: https://www.bam.de/Content/EN/Projects/Beat-Amr/beat-amr.html
3. Flemming H-C, Wingender J, Szewzyk U, Steinberg P, Rice SA, Kjelleberg S. Biofilms: an emergent form of bacterial life. 2016 Sep 1;14(9):563–75. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27510863
4. Centre of Disease Control and Prevention. Pseudomonas aeruginosa in Healthcare Settings [Internet]. 2019. (www.cdc.gov). Available from: https://www.cdc.gov/hai/organisms/pseudomonas.html
5. Bundesanstalt für Materialforschung und -prüfung (BAM). Population dynamics during biofilm formation on antimicrobial surfaces [Internet]. 2022. Available from: https://www.bam.de/Content/EN/Projects/Beat-Amr/beat-amr-bam.html
6. Pietsch F, Heidrich G, Nordholt N, Schreiber F. Prevalent Synergy and Antagonism Among Antibiotics and Biocides in Pseudomonas aeruginosa. 2021 Feb 4;11:615618. Available from: https://www.ncbi.nlm.nih.gov/pubmed/33613467