Eradicating Biofilms: Decoding Persistent Mechanisms and Combating Therapeutic Strategies

Biofilm-associated infections pose a significant clinical challenge to human health due to their high resistance to conventional antibiotics. The formed biofilm of the dense structure can protect the embedded bacteria against antibiotic and immune system attacks. The biofilm microenvironment exhibits unique chemical and physiological heterogeneity, leading to bacterial survival, adaptation, and persistent infection. Herein, this review summarizes the strategies for combating biofilm-associated infections by understanding the resistance mechanisms driven by biofilm characteristics. These strategies include responding to the biofilm microenvironment; disrupting the physiological barrier by chemically polymerizing the biofilm matrix, enzymatically targeting components of extracellular polymeric substances (EPS) production, and penetrating the biofilm barrier using physical methods (e.g., light, sound, magnetic, or electric fields); modulating metabolic changes within biofilm cells; and disrupting quorum sensing and targeting dormant cells. Therefore, this review aims to discuss the current challenges in anti-biofilm therapies and future directions, providing insights for the development of novel anti-biofilm treatments.