title: 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.
authors.affiliation: Department of Chemistry and Biochemistry, and ‡Department of Environmental Health Sciences, University of South Carolina , Columbia, South Carolina 29208, United States.
authors.forename: Jiuyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Yung Pin
authors.initials: YP
authors.lastname: Chen
authors.forename: Kristen P
authors.initials: KP
authors.lastname: Miller
authors.forename: Mitra S
authors.initials: MS
authors.lastname: Ganewatta
authors.forename: Marpe
authors.initials: M
authors.lastname: Bam
authors.forename: Yi
authors.initials: Y
authors.lastname: Yan
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.forename: Alan W
authors.initials: AW
authors.lastname: Decho
authors.forename: Chuanbing
authors.initials: C
authors.lastname: Tang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology; D065093:beta-Lactamase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D011108:Polymers; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases