Understanding and controlling microbial biofilm formation by surface engineering and novel biofilm inhibitors

Microbial biofilms cause serious problems including biocorrosion and biofouling in industrial environments as well persistent infections in clinical settings. As one of the key intrinsic mechanisms, biofilms aggravate the wide spread of antimicrobial resistance. Despite the significant problems caused by biofilms, biofilm formation is still poorly understood and effective control of biofilms remains challenging. In this work, several interdisciplinary approaches were developed and characterized to better understand the fundamentals of biofilm formation and to improve biofilm control. Self-assembled monolayers (SAMs) were applied to obtain well-defined surfaces with tunable inertness to microbial adhesion and biofilm formation by changing the functional groups of SAMs. By applying this useful platform, micro-patterns of surface chemistry were obtained to study microbe-surface interactions at the molecular and cellular levels. D-mannitol-terminated SAM was found to have unprecedented inertness to biofilm formation (up to 26 days). In addition, the data of patterned biofilm formation suggest that a critical distance may exist, beyond which bacteria cannot interact appropriately between clusters in biofilm formation. In addition to the fundamental study, several approaches were also explored to better control biofilms. First, brominated furanones (BFs) and cationic antimicrobial peptides (AMPs) were investigated as novel biofilm inhibitors. Several new BFs were found to have potent inhibitory effects on biofilm formation at the concentrations noninhibitory to planktonic growth of Gram-negative bacteria. The data led to identification of important structural elements of BFs for biofilm control. Hexameric, octameric, and dendrimeric peptides with Trp/Arg repeats also exhibited strong inhibitory effects on biofilm formation. Octameric peptide was also found to be a possible biofilm dispersion agent. It removed and killed up to 95.4% of E. coli biofilm cells from a stainless steel surface at 200 μM. Furthermore, a biocompatible nanofibrous scaffold containing ionic silver was demonstrated to resist biofilm formation for 14 days with controlled release of silver ions. These data provide new insights for understanding biofilm formation and developing biofilm control with enhanced prolonged efficacy.