title: Self-assembled arginine-rich peptides as effective antimicrobial agents.
abstract: Bacteria can adapt to their ever-changing environment to develop a resistance to commonly used antibiotics. This escalating evolution of bacteria coupled with a diminished number of effective antibiotics has caused a global healthcare crisis. New antimicrobials and novel approaches to tackle this problem are urgently needed. Antimicrobial peptides are of particular interest in this endeavor due to their broad spectrum antimicrobial properties as well as ability to combat multi-drug resistant bacteria. Most peptides have both hydrophobic and hydrophilic regions that enable them to be soluble in an aqueous solution, yet can insert into and subsequently disintegrate lipid rich membranes through diverse mechanisms. In this study, a novel class of cationic nanoparticles (formed by the self-assembly of an amphiphilic peptide) were shown to have strong antimicrobial properties against gram-positive bacteria, specifically Staphylococcus aureus, Staphylococcus epidermidis, and methicillin-resistant Staphylococcus aureus (MRSA) with minimal toxicity to human dermal fibroblasts. The particular self-assembled structure tested here included an arginine rich nanoparticle (C17H35GR7RGDS or amphiphilic peptide nanoparticles, APNPs) which incorporated seven arginine residues (imparting a positive charge to improve membrane interactions), a hydrophobic block which drove the self-assembly process, and the presence of an amino acid quadruplet arginine-glycine-aspartic acid-serine (RGDS) which may render these nanoparticles capable of attracting healthy cells while competing bacterial adherence to fibronectin, an adhesive protein found on cell surfaces. As such, this in vitro study demonstrated that the presently formulated APNPs should be further studied for a wide range of antibacterial applications where antibiotics are no longer useful. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1046-1054, 2017.
authors.affiliation: Department of Chemical Engineering, Northeastern University, Boston, Massachusetts.
authors.forename: Gujie
authors.initials: G
authors.lastname: Mi
authors.affiliation: Department of Chemical Engineering, Northeastern University, Boston, Massachusetts.
authors.forename: Di
authors.initials: D
authors.lastname: Shi
authors.affiliation: Parios Regenerative Sciences Inc, Concord, Massachusetts.
authors.forename: Whitney
authors.initials: W
authors.lastname: Herchek
authors.affiliation: Department of Chemical Engineering, Northeastern University, Boston, Massachusetts.|Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Webster
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000254:growth & development*; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013212:Staphylococcus epidermidis / Q000254:growth & development*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D009842:Oligopeptides; C046617:arginyl-glycyl-aspartyl-serine
keywords: antimicrobial peptide; bacteria delayed growth; drug resistance; gram positive bacteria; peptide nanoparticles