Cationic Branched Polyethylenimine (BPEI) Disables Antibiotic Resistance in Methicillin-Resistant Staphylococcus epidermidis (MRSE)

ChemMedChem. 2018 Oct 22;13(20):2240-2248. doi: 10.1002/cmdc.201800433. Epub 2018 Sep 25.

Abstract

Staphylococcus epidermidis is one of the most prevalent prokaryotic species on human skin and mucosal membranes that constitute the commensal flora. S. epidermidis has become one of the most common causes of primary bacteremia. Infections are difficult to diagnose because the pathogen has natural niches on human skin and the ability to adhere to inanimate surfaces via biofilms. Alarmingly, S. epidermidis has acquired resistance to many antibiotics, which presents a danger to human health. Known as methicillin-resistant S. epidermidis (MRSE), most clinical isolates of MRSE in North America exhibit β-lactam resistance primarily due to the presence of mecA, a gene that bestows β-lactam antibiotic resistance in a manner similar to methicillin-resistant Staphylococcus aureus (MRSA). MecA encodes for expression of penicillin-binding protein 2a (PBP2a), which is absent in β-lactam susceptible strains of S. epidermidis. We can disable this resistance factor in MRSE with 600-Da branched polyethylenimine (BPEI). Cationic BPEI targets anionic wall teichoic acid (WTA), an essential cofactor for proper functioning of PBP2a. We found that BPEI synergizes the activity of β-lactam antibiotics against MRSE. Growth curves suggest that the combination of BPEI and oxacillin is bactericidal. Electron micrographs indicate abnormalities in the cellular septa and cell walls of treated samples. Therefore, first-line clinical treatments can be effective against MRSE when used in combination with BPEI.

Keywords: Staphylococcus epidermidis; antibiotic resistance; branched polyethylenimine; wall teichoic acid; β-lactams.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors
  • Cell Wall / drug effects
  • Drug Synergism
  • Methicillin Resistance / drug effects*
  • Microbial Sensitivity Tests
  • Oxacillin / pharmacology
  • Penicillin-Binding Proteins / antagonists & inhibitors
  • Polyethyleneimine / pharmacology*
  • Staphylococcus epidermidis / drug effects*
  • Teichoic Acids / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Penicillin-Binding Proteins
  • Teichoic Acids
  • Polyethyleneimine
  • Oxacillin