Quorum Sensing Peptides Selectively Penetrate the Blood-Brain Barrier

PLoS One. 2015 Nov 4;10(11):e0142071. doi: 10.1371/journal.pone.0142071. eCollection 2015.

Abstract

Bacteria communicate with each other by the use of signaling molecules, a process called 'quorum sensing'. One group of quorum sensing molecules includes the oligopeptides, which are mainly produced by Gram-positive bacteria. Recently, these quorum sensing peptides were found to biologically influence mammalian cells, promoting i.a. metastasis of cancer cells. Moreover, it was found that bacteria can influence different central nervous system related disorders as well, e.g. anxiety, depression and autism. Research currently focuses on the role of bacterial metabolites in this bacteria-brain interaction, with the role of the quorum sensing peptides not yet known. Here, three chemically diverse quorum sensing peptides were investigated for their brain influx (multiple time regression technique) and efflux properties in an in vivo mouse model (ICR-CD-1) to determine blood-brain transfer properties: PhrCACET1 demonstrated comparatively a very high initial influx into the mouse brain (Kin = 20.87 μl/(g×min)), while brain penetrabilities of BIP-2 and PhrANTH2 were found to be low (Kin = 2.68 μl/(g×min)) and very low (Kin = 0.18 μl/(g×min)), respectively. All three quorum sensing peptides were metabolically stable in plasma (in vitro) during the experimental time frame and no significant brain efflux was observed. Initial tissue distribution data showed remarkably high liver accumulation of BIP-2 as well. Our results thus support the potential role of some quorum sensing peptides in different neurological disorders, thereby enlarging our knowledge about the microbiome-brain axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / metabolism*
  • Biological Transport
  • Blood-Brain Barrier*
  • Brain / metabolism*
  • Female
  • Humans
  • Mice
  • Mice, Inbred ICR
  • Microbiota / physiology*
  • Peptide Fragments / pharmacokinetics*
  • Plasma / metabolism*
  • Quorum Sensing / physiology*
  • Tissue Distribution

Substances

  • Peptide Fragments

Grants and funding

This work was supported by the Special Research Fund of Ghent University (www.ugent.be, Grant numbers BOF 01J22510 to BDS and EW, and BOF 01D38811 to SS) and the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen, www.iwt.be, Grant numbers 121512 to BG and 131356 to FV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.