Ultrashort self-assembling Fmoc-peptide gelators for anti-infective biomaterial applications

Biomaterial related infections have a significant impact on society and are a major contributor to the growing threat of antimicrobial resistance. Current licensed antibiotic classes struggle to breakdown or penetrate the exopoly saccharide biofilm barrier, resulting insub-therapeutic concentrations of antibiotic at the surface of the biomaterial, treatment failure and increased spread of resistant isolates. This paper focuses for the first time on the ability of ultrashort Fmoc-peptide gelators to eradicate established bacterial biofilms implicated in a variety of medical device infections (Gram-positive: Staphylococcus aureus, Staphylococcusepidermidis and Gram-negative Escherichia coli, Pseudomonas aeruginosa). The effect of increasing the cationicity of the FmocFF via addition of di-lysine and di-orntithine was alsostudied with regard to antibacterial activity. Our studies demonstrated that Fmoc-peptides(FmocFF, FmocFFKK, FmocFFFKK, FmocFFOO) formed surfactant-like soft gels at concentrations of 1% w/v and above using a method of glucono-δ-Lactone pH induction. The majority of Fmoc-peptides (0.5-2% w/v) demonstrated selective action against established(grown for 24 hour) biofilms of Gram-positive and Gram-negative pathogens with FmocFF and FmocFFKK particularly promising. These results are likely to increase the clinical translation of short-peptide gelator platforms within the area of anti-infective biomaterials including as wound dressings and coatings for prostheses, catheters, heart valves and surgical tubes. In the long-term this will lead to wider treatment choices for clinicians and patients involved in the management of medical device infections and reduce the burden of antimicrobial resistance.