Targeting intracellular, multi-drug resistant Staphylococcus aureus with guanidinium polymers by elucidating the structure-activity relationship

Biomaterials. 2019 Oct:217:119249. doi: 10.1016/j.biomaterials.2019.119249. Epub 2019 Jun 18.


Intracellular persistence of bacteria represents a clinical challenge as bacteria can thrive in an environment protected from antibiotics and immune responses. Novel targeting strategies are critical in tackling antibiotic resistant infections. Synthetic antimicrobial peptides (SAMPs) are interesting candidates as they exhibit a very high antimicrobial activity. We first compared the activity of a library of ammonium and guanidinium polymers with different sequences (statistical, tetrablock and diblock) synthesized by RAFT polymerization against methicillin-resistant S. aureus (MRSA) and methicillin-sensitive strains (MSSA). As the guanidinium SAMPs were the most potent, they were used to treat intracellular S. aureus in keratinocytes. The diblock structure was the most active, reducing the amount of intracellular MSSA and MRSA by two-fold. We present here a potential treatment for intracellular, multi-drug resistant bacteria, using a simple and scalable strategy.

Keywords: Antimicrobial; Block copolymers; Intracellular bacteria; RAFT polymerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Ammonium Compounds / pharmacology
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Endocytosis / drug effects
  • Erythrocytes / drug effects
  • Fluorescence
  • Guanidine / chemical synthesis
  • Guanidine / chemistry*
  • Guanidine / pharmacology*
  • Humans
  • Intracellular Space / microbiology*
  • Microbial Sensitivity Tests
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Polymers / pharmacology*
  • Sheep
  • Staphylococcus aureus / drug effects*
  • Structure-Activity Relationship
  • Toxicity Tests


  • Ammonium Compounds
  • Anti-Bacterial Agents
  • Polymers
  • Guanidine