Peptide-grafting lens to prevent bacterial adhesion and biofilm formation

DESCRIPTION (provided by applicant): Background: Adherence of bacteria to the surfaces of contact lens and subsequent biofilm formation play an important role in lens intolerance, acute red eyes, and corneal infection. Biofilm bacteria can usually survive the use of antiseptics and/or antibiotics at concentration 1000 to 1500 times higher than the concentrations needed to kill planktonic cells of the same species. The alarming increase in drug-resistant bacteria also makes a search for novel means of fighting lens related infections imperative. Therefore, it is important to develop contact lens that prevents, and inhibits the formation of biofilm. The primary prevention of biofilm formation is targeted at the prevention of bacterial adhesion. Preliminary Results: Three anti-adhesion peptides identified in our preliminary study have been proved to possess anti-adhesion characteristics on TentaGel lens in vitro; these peptides have no toxicity to human blood cells and bacteria. Our preliminary data also demonstrates that one-bead one-compound (OBOC) combinatorial peptide library is a powerful and reliable approach to identify a single compound against multiple bacterial adhesions and adhesion factors. Statement of Objectives: In this proposed NIH SBIR Phase I research project, we plan to develop long-lasting and broad spectrum anti-adhesion peptides to fight contact lens-related infection. With this in mind, we propose to design, synthesize and screen cyclic OBOC combinatorial libraries to identify anti-adhesion peptides and optimize their anti-adhesion efficacy. Hypothesis: Small cyclic peptides can block bacterial adhesion and prevent biofilm formation at an early stage. Methods: (1) selection of anti-adhesion peptides by 14 days of incubation of fluorescent labeled S. epidermidis, S. aureus and P. aeruginosa with one-bead one-compound cyclic peptide library; (2) decoding of the anti-adhesion beads using Procise 494 Protein Sequencer; (3) perforation of standard structure relationship study and optimization of anti-adhesion peptides; (4) evaluation of anti-adhesion properties on peptide grafting lens; (5) determination of potential toxicities of anti-adhesion peptides by using human corneal epithelial cell line.