title: Antimicrobial Organometallic Dendrimers with Tunable Activity against Multidrug-Resistant Bacteria.
abstract: Multidrug-resistant pathogens are an increasing threat to public health. In an effort to curb the virulence of these pathogens, new antimicrobial agents are sought. Here we report a new class of antimicrobial organometallic dendrimers with tunable activity against multidrug-resistant Gram-positive bacteria that included methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Mechanistically, these redox-active, cationic organometallic dendrimers induced oxidative stress on bacteria and also disrupted the microbial cell membrane. The minimum inhibitory concentrations, which provide a quantitative measure of the antimicrobial activity of these dendrimers, were in the low micromolar range. AlamarBlue cell viability assay also confirms the antimicrobial activity of these dendrimers. Interestingly, these dendrimers were noncytotoxic to epidermal cell lines and to mammalian red blood cells, making them potential antimicrobial platforms for topical applications.
authors.affiliation: Department of Chemistry, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.
authors.forename: Alaa S
authors.initials: AS
authors.lastname: Abd-El-Aziz
authors.affiliation: Department of Chemistry, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Agatemor
authors.affiliation: Department of Chemistry, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.
authors.forename: Nola
authors.initials: N
authors.lastname: Etkin
authors.affiliation: Department of Chemistry, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.|Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.
authors.forename: David P
authors.initials: DP
authors.lastname: Overy
authors.affiliation: Department of Chemistry, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Lanteigne
authors.affiliation: Department of Chemistry, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.
authors.forename: Katherine
authors.initials: K
authors.lastname: McQuillan
authors.affiliation: Department of Chemistry, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.|Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.
authors.forename: Russell G
authors.initials: RG
authors.lastname: Kerr
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D016984:Enterococcus faecium / Q000187:drug effects*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D018384:Oxidative Stress / Q000187:drug effects; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D050091:Dendrimers