title: Quorum Sensing Peptides Selectively Penetrate the Blood-Brain Barrier.
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.
authors.affiliation: Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Wynendaele
authors.affiliation: Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Frederick
authors.initials: F
authors.lastname: Verbeke
authors.affiliation: Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Stalmans
authors.affiliation: Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Gevaert
authors.affiliation: Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Yorick
authors.initials: Y
authors.lastname: Janssens
authors.affiliation: Department of Radiology and Nuclear Medicine, Faculty of Medicine and Health Sciences, Ghent University Hospital, Ghent, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Van De Wiele
authors.affiliation: Department of Medical Imaging, Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peremans
authors.affiliation: Comparative Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Burvenich
authors.affiliation: Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: De Spiegeleer
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D064307:Microbiota / Q000502:physiology*; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D010949:Plasma / Q000378:metabolism*; D053038:Quorum Sensing / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D010446:Peptide Fragments