Targeting biofilms: Current and prospective therapeutics

Biofilm formation is now recognized as a key virulence factor for a wide range of chronic microbial infections. While it has been well known for decades that bacteria and fungi in biofilms become highly tolerant of antibiotics, the development of effective therapeutics has lagged behind our growing understanding of biofilm biology. The multifactorial nature of biofilm development and drug tolerance imposes significant challenges to conventional antimicrobials, and indicates the need for multi-targeted or combinatorial therapies. In light of the discrepancy between the explosion of papers presenting multitude of methods to control biofilms and the sparsity of biofilm specific treatments available to the clinician, in this review, we focus on current therapeutic strategies and those in development for the treatment of biofilm infections, which target vital structure-function traits 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 anti-biofilm technologies, and provide a rationale for multi-targeted therapies aimed at disrupting the complex biofilm microenvironment