This is on-going work. We are currently studying the mechanism by which these materials exert their antibacterial activity. In sum, 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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Ishikawa, Ken; Medina, Scott H; Schneider, Joel P et al. (2017) Glycan Alteration Imparts Cellular Resistance to a Membrane-Lytic Anticancer Peptide. Cell Chem Biol 24:149-158
Yamada, Yuji; Schneider, Joel P (2016) Fragmentation of Injectable Bioadhesive Hydrogels Affords Chemotherapeutic Macromolecules. Biomacromolecules 17:2634-41
Urano, Emiko; Ablan, Sherimay D; Mandt, Rebecca et al. (2016) Alkyl Amine Bevirimat Derivatives Are Potent and Broadly Active HIV-1 Maturation Inhibitors. Antimicrob Agents Chemother 60:190-7
Medina, Scott H; Miller, Stephen E; Keim, Allison I et al. (2016) An Intrinsically Disordered Peptide Facilitates Non-Endosomal Cell Entry. Angew Chem Int Ed Engl 55:3369-72
Medina, Scott H; Schneider, Joel P (2015) Cancer cell surface induced peptide folding allows intracellular translocation of drug. J Control Release 209:317-26
Nagy-Smith, Katelyn; Moore, Eric; Schneider, Joel et al. (2015) Molecular structure of monomorphic peptide fibrils within a kinetically trapped hydrogel network. Proc Natl Acad Sci U S A 112:9816-21
Sonmez, Cem; Nagy, Katelyn J; Schneider, Joel P (2015) Design of self-assembling peptide hydrogelators amenable to bacterial expression. Biomaterials 37:62-72
Giano, Michael C; Ibrahim, Zuhaib; Medina, Scott H et al. (2014) Injectable bioadhesive hydrogels with innate antibacterial properties. Nat Commun 5:4095
Veiga, Ana Salomé; Schneider, Joel P (2013) Antimicrobial hydrogels for the treatment of infection. Biopolymers 100:637-44
Gaspar, Diana; Veiga, Ana Salomé; Sinthuvanich, Chomdao et al. (2012) Anticancer peptide SVS-1: efficacy precedes membrane neutralization. Biochemistry 51:6263-5

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