(222a) Sensitizing Bacterial Cells to Antibiotics through Dynamic Topography–Triggered Biofilm Detachment

Microbial biofilm is a leading cause of chronic infections in humans and persistent biocorrosion and biofouling in industries due to extremely high-level tolerance of biofilm cells to antimicrobial agents. In the past three decades, the significance of biofilms has stimulated extensive studies on strategies for biofilm prevention and removal. However, due to the protection of extracellular matrix and slow growth of biofilm cells, controlling mature biofilm remains challenging. Recently, we reported that mature biofilms can be effectively removed (e.g. 99.9% detachment of 48h Pseudomonas aeruginosa PAO1 biofilms) using shape memory polymer-based dynamic change in surface topography. Here, we demonstrate that such biofilm detachment also sensitizes biofilm cells to conventional antibiotics. For example, concurrent treatment of 48h P. aeruginosa PAO1 biofilms during dynamic biofilm removal increased the susceptibility of released biofilm cells to tobramycin by more than 3 logs (2,479 fold) compared to surface-attached biofilm cells. The observed effects were attributed to the disruption of biofilm structure and increase in cellular activity as evidenced by a 11.8-fold increase in ATP level and 4.1-fold increase in expression of rrnB gene in detached cells. These results can guide the design of future combinational therapies for biofilm removal by integrating newly-designed smart dispersion strategies with currently available antibiotics.