Truncated Autoinducing Peptides as Antagonists of Staphylococcus lugdunensis Quorum Sensing

J Med Chem. 2016 Oct 13;59(19):8879-8888. doi: 10.1021/acs.jmedchem.6b00727. Epub 2016 Sep 15.

Abstract

Competitive quorum sensing (QS) antagonism offers a novel strategy for attenuating current multidrug resistant staphylococcal infections. To this end, a series of 10 truncated analogues based on the parent autoinducing peptides (AIPs) of Staphylococcus lugdunensis (groups I and II) and Staphylococcus epidermidis (groups I-III) were sequentially assessed against a newly developed Staphylococcus lugdunensis group I QS reporter strain. The truncated analogues based upon Staphylococcus lugdunensis AIP-1 (1) and AIP-2 (2) displayed respective IC50 values of 0.2 ± 0.01 μM and 0.3 ± 0.01 μM, while the truncated analogue of the Staphylococcus epidermidis AIP-1 (3) elicited an IC50 value of 2.7 ± 0.1 μM. These findings demonstrate the potential of cognate and "crosstalk" competitive quorum sensing inhibition using truncated AIPs as a means of attenuating staphylococcal infections in species beyond Staphylococcus aureus.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / pharmacology*
  • Drug Discovery
  • Humans
  • Models, Molecular
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology*
  • Quorum Sensing / drug effects*
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcus epidermidis / chemistry
  • Staphylococcus lugdunensis / drug effects*
  • Staphylococcus lugdunensis / physiology

Substances

  • AgrD protein, Staphylococcus
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Peptides, Cyclic