Antimicrobial Organometallic Dendrimers with Tunable\nActivity against Multidrug-Resistant Bacteria

Abstract

Multidrug-resistant\npathogens are an increasing threat to public\nhealth. In an effort to curb the virulence of these pathogens, new\nantimicrobial agents are sought. Here we report a new class of antimicrobial\norganometallic dendrimers with tunable activity against multidrug-resistant\nGram-positive bacteria that included methicillin-resistant <i>Staphylococcus aureus</i> and vancomycin-resistant <i>Enterococcus\nfaecium</i>. Mechanistically, these redox-active, cationic organometallic\ndendrimers induced oxidative stress on bacteria and also disrupted\nthe microbial cell membrane. The minimum inhibitory concentrations,\nwhich provide a quantitative measure of the antimicrobial activity\nof these dendrimers, were in the low micromolar range. AlamarBlue\ncell viability assay also confirms the antimicrobial activity of these\ndendrimers. Interestingly, these dendrimers were noncytotoxic to epidermal\ncell lines and to mammalian red blood cells, making them potential\nantimicrobial platforms for topical applications.