THE DESIGN OF EFFECTIVE ANTI-BIOFILM AGENTS

Pathogenic infections represent a persistent threat to human health. In addition to the ability of the bacteria to develop resistance very rapidly, many of the bacteria form biofilms. Biofilm is defined as structured aggregation of surface-attached bacteria encased in an extracellular matrix that leads to bacterial resistance to antibiotics. The difficulty of successfully treating biofilm and the increasing resistance of microbes to traditional treatments demands for the discovery of compounds with novel mode of action to tackle this threat. Host-Defense Peptides (HDPs) are produced by eukaryotes as part of the innate immune response to bacterial infection. These agents represent a potential source of inspiration for development of new antibacterial agents but less is known about their ability to prevent biofilm formation. The broad molecular diversity among HDPs suggests that their activity is not tightly coupled to specific features of amino acid sequence or peptide conformation. This situation has motivated us to develop antimicrobial sequence-random hydrophobic-cationic peptides using solid-phase synthesis in an unconventional way. We studied their ability to prevent biofilm formation either by inhibiting the initial bacterial adhesion to the surface or by the removal of the established biofilm. According to our findings the random peptide mixtures were able to control and manage biofilm and might be used as lead biofilm inhibitors candidate for further studies.