Modulation of Quorum Sensing in a Gram-Positive Pathogen by Linear Molecularly Imprinted Polymers with Anti-infective Properties

Angew Chem Int Ed Engl. 2017 Dec 22;56(52):16555-16558. doi: 10.1002/anie.201709313. Epub 2017 Dec 1.

Abstract

We describe the development, characterization, and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as an anti-infective by blocking the quorum sensing (QS) mechanism and so abrogating the virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches, no cross-linker is used. This results in soluble low-molecular-weight oligomers that can act as a therapeutic agent in vitro and in vivo. The LMIP was characterized by mass spectrometry to determine its monomer composition. Fragments identified were then aligned along the peptide template by computer modeling to predict the possible monomer sequence of the LMIP. These findings provide a proof of principle that LMIPs can be used to block QS, thus setting the stage for the development of LMIPs a novel drug-discovery platform and class of materials to target Gram-positive pathogens.

Keywords: antibacterial agents; molecular imprinting; quorum sensing; receptors; virulence factors.

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Bacterial Proteins / chemistry
  • Mass Spectrometry
  • Molecular Imprinting
  • Peptides / chemistry
  • Peptides / metabolism
  • Polymers / chemistry*
  • Quorum Sensing / drug effects*
  • Streptococcus pneumoniae / physiology*
  • Virulence / drug effects

Substances

  • ATP-Binding Cassette Transporters
  • Anti-Infective Agents
  • Bacterial Proteins
  • Peptides
  • Polymers