Clinical Translation of Biofilm Dispersal Agents

Abstract

The global problem of chronic infection is enormous and increasing. Combined with the challenge that antibiotic resistance already poses, the task of developing new agents that address chronic infection is arduous. As biofilms are a major strategy used by microbes to evade the immune response and antibiotics, developing therapeutics that prevent or destroy biofilms has become a major focus for many researchers. One promising anti-biofilm strategy is to release or disperse cells from the biofilm, which better exposes them to antimicrobial agents. Dispersal can be accomplished with a variety of agents that can initiate either active or passive dispersal, and many of these agents are in preclinical or clinical development. Yet, significant hurdles exist for the clinical translation of biofilm dispersal agents. Regulatory requirements are ambiguous and daunting and can present major roadblocks. There are also real therapeutic risks for dispersing bacteria during active infection, including sepsis and even death. However, proof of concept studies have provided evidence that dispersal can be combined with antibiotics for an effective and safe treatment. As our understanding of dispersal increases, better models are developed, and dispersal agents are refined, it is likely that we will achieve more success in translating the strategy of biofilm dispersal into the clinic.