Targeting microbial biofilms: current and prospective therapeutic strategies

Biofilms harbour complex structural and biological attributes, such as the presence of an extracellular polymeric matrix, physical and chemical heterogeneity and drug tolerance, which provide remarkable therapeutic challenges.Biofilm drug tolerance is a consequence of complex physicochemical and biological properties with multiple microbial genetic and molecular factors, often involving polymicrobial interactions.The challenges to existing antimicrobial or monotherapeutic approaches by the multifactorial nature of biofilm development, combined with drug tolerance, requires robust effective multitargeted or combinatorial therapies.Combinatorial strategies are needed to eliminate existing biofilms by targeting vital structural and functional traits of biofilms, such as the EPS matrix and dormant cells, as well as approaches exploiting host–pathogen interactions.Promising technologies based on 'smart release' or 'on-demand activation' of bioactive agents when triggered by biofilm-derived cues can degrade the matrix and kill resident bacteria, and have the potential to eradicate the pathogenic niche with precision and minimal cytotoxicity to surrounding tissues.Validation of proof-of-concept studies using clinically relevant animal models, as well as clinical trials, are needed for rigorous evaluation.