Antibiofilm molecules do not directly target bacterial cells but can interfere with biofilm formation.
Due to biofilm recalcitrance to antibiotics, alternative approaches under investigation are focused on limiting cell adhesion, controlling biofilm growth, degrading its matrix to enhance penetration of antimicrobial molecules, reducing its viability, and removing health-impacting biofilms [i,ii,iii,iv]. These strategies aim to improve antibiotic efficacy and bypass the inability of antibiotic molecules to completely eradicate biofilms [v]. Strategies under investigation in basic research studies include a plethora of anti-biofilm agents, proposed to specifically impact different aspects of biofilm life. For example, quorum sensing (QS) inhibitors or modulators can hamper bacterial communications required to coordinate biofilm formation, limiting bacterial adhesions with different modes of action [vi];
EPS production inhibitors impair matrix synthesis; and degrading agents reduce biofilm burden [vii].
However, these approaches are still scarcely represented in clinical trials, as their efficacy and toxicity are still under evaluation in vivo in preclinical models [viii]. QS inhibitors possess several favorable characteristics, such as low molecular weight, high specificity, no adverse events on the host, high stability and resistance to host metabolism, and no impact on the microbiome, as described in Kalia et al, 2019. However, their efficacy must be tested against clinical isolates [ix]. Biofilm matrix components are investigated due to their critical importance in biofilm biology and are considered viable targets for development of new drugs that could play a crucial role in tackling biofilms [x]. Additional animal models need to be developed to simulate human infections and understand how EPS is produced in vivo and how it influences the interactions between bacteria and the host immune system [xi].
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