Antimicrobial metallopolymers and their bioconjugates with conventional antibiotics against multidrug-resistant bacteria

J Am Chem Soc. 2014 Apr 2;136(13):4873-6. doi: 10.1021/ja5011338. Epub 2014 Mar 20.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Humans
  • Hydrolysis
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / enzymology
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology
  • Polymers / chemistry
  • Polymers / pharmacology
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / enzymology
  • Staphylococcal Infections / microbiology
  • beta-Lactamase Inhibitors / chemistry*
  • beta-Lactamase Inhibitors / pharmacology*
  • beta-Lactamases / metabolism
  • beta-Lactams / chemistry
  • beta-Lactams / pharmacology

Substances

  • Anti-Bacterial Agents
  • Organometallic Compounds
  • Polymers
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • beta-Lactamases