Antimicrobial Metallopolymers and Their Bioconjugates with Conventional Antibiotics against Multidrug-Resistant Bacteria

Abstract

Bacteria are now becoming more resistant to most conventional antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA), a complex of multidrug-resistant Gram-positive bacterial strains, has proven especially problematic in both hospital and community settings by deactivating conventional β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, through various mechanisms, resulting in increased mortality rates and hospitalization costs. Here we introduce a class of charged metallopolymers that exhibit synergistic effects against MRSA by efficiently inhibiting activity of β-lactamase and effectively lysing bacterial cells. Various conventional β-lactam antibiotics, including penicillin-G, amoxicillin, ampicillin, and cefazolin, are protected from β-lactamase hydrolysis via the formation of unique ion-pairs between their carboxylate anions and cationic cobaltocenium moieties. These discoveries could provide a new pathway for designing macromolecular scaffolds to regenerate vitality of conventional antibiotics to kill multidrug-resistant bacteria and superbugs.

Controlling macromolecular structures towards effective antimicrobial polymers

“…Tang and coworkers recently reported a class of novel charged metallopolymers based on cationic cobaltocenium-containing polymers that were bactericidal and highly biocompatible [157]. Cobaltocenium-containing methacrylate polymers with hexafluorophosphate anion and their halide paired cobaltoceniumcontaining polymers were synthesized via RAFT polymerization and further ion exchange.…”

Main-chain metallopolymers at the static–dynamic boundary based on nickelocene

“…4,5 This diversity in structure and dynamics has facilitated a myriad of applications that include self-healing, 6,7 light emission, 8,9 photovoltaics, 10,11 stimuli-responsive behaviour, 12,13 catalysis, 14 information storage, 15 antibacterial activity, 16 and nanopatterning. [17][18][19] Main-chain polymetallocenes based on ferrocene, such as polyferrocenylsilanes (PFSs) ( Fig.…”

Antimicrobial Organometallic Dendrimers with Tunable Activity against Multidrug-Resistant Bacteria

“…[10][11][12][13][14] Synthetic organometallic antimicrobial agents are structurally unique, leading to new mechanism of action that bypass resistance mechanism, ultimately resulting in potent activity against multidrug-resistant microbes. Regrettably, research on this class of antimicrobial is still at the early stage, 15 focusing 4 on small molecules or conventional macromolecular scaffolds, 11 and consequently, the unexplored potential of this class still needs to be evaluated.…”