Norepinephrine and Serotonin Can Modulate the Behavior of the Probiotic Enterococcus faecium NCIMB10415 towards the Host: Is a Putative Surface Sensor Involved?

Rossella Scardaci,Tiziana Musso,Sara Scutera,Olivier Lesouhaitier,Nathalie Connil,Francesca Bietto,Amine M. Boukerb,Enrica Pessione,Pierre-Jean Racine,Marc G. J. Feuilloley

doi:10.3390/microorganisms10030487

Rossella Scardaci, Tiziana Musso + Show 8 more

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https://doi.org/10.3390/microorganisms10030487

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Abstract

The human gut microbiota has co-evolved with humans by exchanging bidirectional signals. This study aims at deepening the knowledge of this crucial relationship by analyzing phenotypic and interactive responses of the probiotic Enterococcus faecium NCIMB10415 (E. faecium SF68) to the top-down signals norepinephrine (NE) and serotonin (5HT), two neuroactive molecules abundant in the gut. We treated E. faecium NCIMB10415 with 100 µM NE and 50 µM 5HT and tested its ability to form static biofilm (Confocal Laser Scanning Microscopy), adhere to the Caco-2/TC7 monolayer, affect the epithelial barrier function (Transepithelial Electrical Resistance) and human dendritic cells (DC) maturation, differentiation, and cytokines production. Finally, we evaluated the presence of a putative hormone sensor through in silico (whole genome sequence and protein modelling) and in vitro (Micro-Scale Thermophoresis) analyses. The hormone treatments increase biofilm formation and adhesion on Caco-2/TC7, as well as the epithelial barrier function. No differences concerning DC differentiation and maturation between stimulated and control bacteria were detected, while an enhanced TNF-α production was observed in NE-treated bacteria. Investigations on the sensor support the hypothesis that a two-component system on the bacterial surface can sense 5HT and NE. Overall, the data demonstrate that E. faecium NCIMB10415 can sense both NE and 5HT and respond accordingly.

Highlights

Our group already assessed the biofilm formation ability of E. faecium NCIMB10415 with the crystal violet method in control and stimulated conditions, and both molecules caused a significant enhancement of biomasses after the treatment [22,23]
The Transepithelial Electrical Resistance (TER) experiment intended to evaluate gut cell permeability on differentiated cells demonstrated that the stimulation was beneficial, since the treated bacteria increased the host’s barrier function significantly more than the control cultures of Enterococcus NCIMB10415
Interesting results on the interaction between HK bacteria and dendritic cells (DC) were obtained: even if the hormone treatments had no effect on the strain ability to induce DC maturation and differentiation, the production of the pro-inflammatory TNF-α by DCs challenged with NE-treated HK cells was significantly higher than in control conditions

Summary

Introduction

In addition to starter strains employed in food production [4], biocontrol strains [5], putative [6,7,8] and approved probiotics commercially available for human and animals’ treatment [2,9], several hospital strains displaying both antibiotic resistance and production of virulence factors have been isolated so far [10,11] These are among the most diffused opportunistic nosocomial pathogens involved in severe diseases such as urinary infections, endocarditis, bacteremia, and central nervous system infections [12]. These bacteria bear in their genomes multidrug resistance genes [13,14] and the so-called pathogenicity island, which

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