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Resistance Proof Antibiotic Mechanism Found

In an increasingly global society, fears of superbugs appear more salient than ever. One German study, for example, found that of the 187 E. coli strains examined from five different airports, ninety percent were resistant to at least one antibiotic (Heß et al. 2019). As antimicrobial resistance moves closer to the pre-antibiotic era and transmissions between countries increases rapidly, new bacterial inhibition strategies are more needed than ever before.

New research conducted by KU Leuven, Oxford, and Duquesne University, largely funded by the KU Leuven research fund and EU research grants1 details a mechanism that inhibits the growth of bacteria and facilitates their mechanical removal, treatment with conventional antibiotics, and elimination by the host’s immune system (Dieltjens et al. 2020). This mechanism employs a chemically synthesized inhibitor formulated at KU Leuven in a past study (Robijns et al. 2014). The compound inhibits the production of a dense, surface-bound matrix communally created by bacteria called biofilm. (Dieltjens et al. 2020). The biofilm disruption is highly relevant because bacteria with biofilm are up to one-thousand times more tolerant to antibiotics. 

The study found that biofilm inhibition is an effective measure to combat microbial resistance because it suppressed biofilm development and rendered bacteria susceptible to external intervention and treatment. This research built off social evolution theory of bacterial colonies, which predicts that inhibiting public or communal goods, such as bacterial biofilm, suppresses bacterial growth and survival. Thus, the researchers hypothesized that biofilms were the ideal target to restrain bacterial growth (Drescher et al. 2014). 

Furthermore, with inevitable bacterial resistance in mind, the scientists focused on a mechanism that did not favor resistance by natural selection. The scientists thus decided to focus on bacterial common goods because they are intensive for some bacteria to produce but benefit other members of the population as well (Dieltjens et al. 2020). 

To connect the idea of public goods and antibiotic resistance, strains resistant to a public good inhibitor, in this case, the inhibition of biofilm production, will continue to produce the public good at a high cost. The nonresistant strains will receive the protection of the constructed biofilm and eventually outcompete and eliminate the resistant bacteria because they are not taxed by producing the biofilm. As a result, the bacterial colony will collapse and the susceptible bacteria can be more easily treated. 

During their study, the researchers first established that increased biofilm formation promotes antibiotic tolerance and that the production of a biofilm is costly to some cells and beneficial to others. For example, while salmonella without a biofilm are highly susceptible to hydrogen peroxide, those with a biofilm were more tolerant. Furthermore, to establish that biofilms are indeed shared between cells, the researchers noted the strain colors of resistant and nonresistant bacteria and cultured them together. The colony was formed by a mixture of the two colors, which indicates that the biofilm protected both strains of salmonella, proving that biofilms are a shared public good.

With biofilm established as a public good, the authors then ensured that the previously synthesized biofilm inhibitor was resistant proof. The authors conjectured that nonresistant bacteria must benefit from the shared biofilm so much that they eventually outcompete the resistant bacteria and cause the collapse of the biofilm building population. The scientists grew the two strains together and as expected the population of resistant bacteria decreased and the nonresistant bacteria outcompeted the resistant strain in all cases, which verified their hypothesis. 

Finally, the authors established that resistance does not evolve to the inhibition of bacterial biofilms, the researchers conducted an evolution experiment that only cultured cells attached to the bacterial biofilm because those cells were the ones producing the protective layer. After twenty iterations, salmonella populations still did not exhibit any resistance to biofilm disruption, illustrating the mechanism’s resistant proof nature. 

In sum, the study importantly established that in the treatment of resistant salmonella, biofilm disruption is a strategy that works against resistant bacteria and is a mechanism that does not give rise to resistant bacteria, which is a major innovation in this antimicrobial research. This study is ethical and it will importantly improve the health and wellbeing of populations worldwide.  

Importantly, the work of this study is consistent with previous work studying P. fluorescens and Bacillus subtilis that shows biofilms are cooperative products, which demonstrates the robust effects of biofilm disruption to treat bacterial resistance in other types of bacteria (Rainey and Rainey 2003; Van Gestel et al. 2014). 

The next steps for similar antimicrobial research may include further exploring biofilm inhibition as a method to inhibit bacteria and avoid selection for antibiotic resistance. The authors acknowledge that studies shown not all bacteria are suitable for biofilm inhibition because certain bacteria that create biofilms evolve to compete with the nonproducers by providing themselves with superior positions in the biofilm. Thus, the scope of functionally for the discovered treatment must be further explored and clarified (Nadell et al. 2016). Finally, this study may be easily repeated as the authors include all data and methods in their published work. Replication will expand the validity of the findings.



1. For a complete list of funding see the acknowledgments section of study


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