Review explores innovative strategies to overcome microbial persistence within resilient biofilm structures

Biofilms represent a major challenge in clinical and industrial settings due to their complex architecture and physiological heterogeneity, which confer exceptional tolerance to antimicrobials. Current treatments often fail against these resilient microbial communities, leading to chronic and recurrent infections. This persistence is driven by mechanisms like EPS protection, quorum sensing, and the formation of dormant persister cells, which are genetically susceptible but phenotypically tolerant to antibiotics.

This review synthesizes current knowledge on the molecular mechanisms underpinning biofilm resilience and microbial persistence. It systematically analyzes various strategies aimed at disrupting biofilm structures and eliminating persister cells. The authors explore diverse approaches, including novel antimicrobial agents, biofilm-dispersing enzymes, and strategies targeting bacterial communication (quorum sensing).

The review highlights that approximately 80% of chronic and recurrent bacterial infections are linked to biofilms, which protect bacteria from antibiotics and immune effectors. It details how EPS-mediated protection, quorum sensing (QS), and metabolic alterations contribute to this resilience. A key insight is the physiological heterogeneity within biofilms, creating subpopulations from metabolically active to dormant persister cells.

"Persister cells are transient, phenotypic variants within bacterial populations that remain genetically antibiotic-susceptible but survive antimicrobial exposure by entering a dormant or slow-growing physiological state." These persister cells are particularly abundant in biofilms, where nutrient limitation further promotes their formation and tolerance through metabolic inactivity and stress-response activation.