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Targeting microbial biofilms: current and prospective therapeutic strategies
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Journal Article
Targeting microbial biofilms: current and prospective therapeutic strategies
2017
Overview
Key Points
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.
In this Review, Stoodley and colleagues discuss current therapeutic strategies and those under development for the treatment of pathogenic biofilms. They explore novel technologies that promise to enhance the efficacy of current therapeutics or provide novel effects and argue that treating biofilm infections requires combination therapies.
Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections. The multifactorial nature of biofilm development and drug tolerance imposes great challenges for the use of conventional antimicrobials and indicates the need for multi-targeted or combinatorial therapies. In this Review, we focus on current therapeutic strategies and those under development that target vital structural and functional traits of microbial biofilms and drug tolerance mechanisms, including the extracellular matrix and dormant cells. We emphasize strategies that are supported by
in vivo
or
ex vivo
studies, highlight emerging biofilm-targeting technologies and provide a rationale for multi-targeted therapies aimed at disrupting the complex biofilm microenvironment.
Publisher
Nature Publishing Group UK,Nature Publishing Group
