Green Molecules on Red Alert: Amino Acid-Based Surfactants as Sustainable Antimicrobials Against Biofilms

Bacterial biofilms are structured microbial communities embedded in a self-produced extracellular matrix, displaying enhanced tolerance and, in many cases, resistance to biocides, antimicrobial agents, and host immune responses. These traits make biofilms a major driver of chronic and recurrent infections, which are increasingly difficult to eradicate and represent a significant global health challenge in the context of rising antimicrobial resistance (AMR). Biofilms are recognized as surface and nonsurface-attached aggregates in diverse clinical, industrial, and environmental settings, broadening our knowledge of their ecological and physiological diversity. Surfactants have emerged as promising antibiofilm agents due to their dual functionality: the capacity to disrupt the extracellular matrix and their inherent antimicrobial activity. Among them, amino acid-based surfactants, particularly cationic derivatives such as those based on arginine, combine potent biocidal effects with favorable biocompatibility and environmental sustainability. These compounds offer a persuasive alternative to conventional biocides, which often promote cross-resistance and environmental concerns. This review integrates current knowledge of biofilm formation and persistence with advances in the development and application of amino acid-based surfactants as antibiofilm agents. Sustainable synthesis of these compounds, as well as mechanistic insights, and the translational challenges of moving from in vitro assays to real-world scenarios in the AMR era.