title: Antibacterial Low Molecular Weight Cationic Polymers: Dissecting the Contribution of Hydrophobicity, Chain Length and Charge to Activity.
abstract: The balance of cationicity and hydrophobicity can profoundly affect the performance of antimicrobial polymers. To this end a library of 24 cationic polymers with uniquely low degrees of polymerization was synthesized via Cu(0)-mediated polymerization, using three different cationic monomers and two initiators: providing two different hydrocarbon chain tail lengths (C2and C12). The polymers exhibited structure-dependent antibacterial activity when tested against a selection of bacteria, viz,Staphylococcus aureusATCC 29213,Klebsiella pneumoniaeATCC 13883,Acinetobacter baumanniiATCC 19606, andPseudomonas aeruginosaATCC 27853 as a representative palette of Gram-positive and Gram-negative ESKAPE pathogens. The five best-performing polymers were identified for additional testing against the polymyxin-resistantA. baumanniiATCC 19606R strain. Polymers having the lowest DP and a C12hydrophobic tail were shown to provide the broadest antimicrobial activity against the bacteria panel studied as evidenced by lower minimum inhibitory concentrations (MICs). An optimal polymer composition was identified, and its mechanism of action investigated via membrane permeability testing againstEscherichia coli. Membrane disruption was identified as the most probable mechanism for bacteria cell killing.
authors.affiliation: Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, 381 Royal Pde, Parkville, VIC, AUSTRALIA, 3052.
authors.forename: James L
authors.initials: JL
authors.lastname: Grace
authors.affiliation: Institute of Molecular Biosciences, The University of Queensland, Brisbane QLD Australia 4072.
authors.forename: Johnny X
authors.initials: JX
authors.lastname: Huang
authors.affiliation: Monash Institute of Pharmaceutical Sciences, 381 Royal Pde, Parkville, VIC, AUSTRALIA, 3052.
authors.forename: Soon-Ee
authors.initials: SE
authors.lastname: Cheah
authors.affiliation: Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, 381 Royal Pde, Parkville, VIC, AUSTRALIA, 3052.
authors.forename: Nghia P
authors.initials: NP
authors.lastname: Truong
authors.affiliation: Institute of Molecular Biosciences, The University of Queensland, Brisbane QLD Australia 4072.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.affiliation: Monash Institute of Pharmaceutical Sciences, 381 Royal Pde, Parkville, VIC, AUSTRALIA, 3052.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, 381 Royal Pde, Parkville, VIC, AUSTRALIA, 3052.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Davis
authors.affiliation: Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, 381 Royal Pde, Parkville, VIC, AUSTRALIA, 3052.
authors.forename: John F
authors.initials: JF
authors.lastname: Quinn
authors.affiliation: Monash Institute of Pharmaceutical Sciences, 381 Royal Pde, Parkville, VIC, AUSTRALIA, 3052.
authors.forename: Tony
authors.initials: T
authors.lastname: Velkov
authors.affiliation: Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, 381 Royal Pde, Parkville, VIC, AUSTRALIA, 3052.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Whittaker