Development of antibacterial agents and materials

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

We have designed a family of peptide-based hydrogels, whose material surfaces can actively kill Gram-positive (Staphylococcus epidermidis, Staphylococcus aureus, and Streptococcus pyogenes) and Gram-negative (Klebsiella pneumoniae and Escherichia coli) bacteria, all prevalent in hospital settings. The significance of these materials is that they can be used as drug delivery vehicles as well as extracellular matrix substitutes that are inherently antibacterial, thus significantly limiting infection during administration. Recently, we have prepared a potent hydrogel from a peptide, named MARG1, which is active against Methicillin-resistant Staphylococcus aureus (MRSA). Although these hydrogel surfaces, in general, exhibit bactericidal activity, our results indicate that their surfaces are non-hemolytic toward human erythrocytes and non-cytotoxic toward mammalian cells. We have shown that MARG1 gels can kill up to 100,000,000 colony forming units of MRSA introduced to each square decimeter of the hydrogels surface. MARG1 hydrogels can be shear-thin delivered by syringe allowing easy administration. The hydrogel can be applied to clean surfaces to inhibit potential infections, and in addition, can be delivered to an infected site where bacterial cells are killed on contact. We are currently establishing structure/activity relationships and studying the mechanism of action of these peptide-based materials. This will allow us to use structure-based design procedures to generate a new generation of peptide-based gels with improved antibacterial activity and biocompatibility.