Small molecules as next generation biofilm inhibitors and anti-infective agents

Abstract

Abstract Biofilms are consortia of microbes attached to surfaces that could be biotic or abiotic in nature. The bacterial cells are enclosed within a microbial synthesized extrapolymeric substances (EPS). The presence of a thick EPS matrix around the cells, protects it from antimicrobials. As the biofilms are difficult to be eradicated in the tissues and implants, the infections due to biofilms are chronic, persistent as well as recurrent in nature. Biofilm formation in multidrug resistant pathogens is a major public health concern. In this review, we have discussed traditional drug discovery approaches and high throughput screening assays involved in the discovery of small molecules for their application as biofilm inhibitory agents. The small molecules target different phases of biofilm growth in pathogenic bacteria. Here, we have focused on three specific application of small molecules, as anti-adhesion agents that prevent adherence and attachment of cells to surfaces; signal inhibitors that disrupt communication between cells resulting in hampered biofilm growth and development; and finally as agents that induce release of cells from mature biofilms. Some of the biofilm inhibitors have also potentiated the antibiotic efficacy leading to complete eradication of biofilms. It is highly pertinent now to focus on developing these as therapeutics and anti-biofilm agents for coating medical implants and devices in clinical settings.