Influence of Catecholamines (Epinephrine/Norepinephrine) on Biofilm Formation and Adhesion in Pathogenic and Probiotic Strains of Enterococcus faecalis

Abstract

<i>Enterococcus faecalis</i> has controversial status due to its emerging role in nosocomial infections, while some strains with beneficial effects are used as probiotics and starter cultures in dairy industry. These bacteria can be found as resident or transient germs in the gut or on skin, where they are continually exposed to various eukaryotic molecules. In this context, the aim of our work was to evaluate the effect of the catecholamine stress hormones, epinephrine (Epi), and norepinephrine (NE) on some <i>Enterococcus s</i>trains. Four <i>E. faecalis</i> strains were included in this study: <i>E. faecalis</i> MMH594 and <i>E. faecalis</i> V583, pathogenic strains of clinical origin, <i>E. faecalis</i> Symbioflor 1 clone DSM 16431, a pharmaceutical probiotic, and <i>E. faecalis</i> OB15, a probiotic strain previously isolated from Tunisian rigouta (Baccouri et al., 2019). Epi was found to modulate the formation of biofilm (biovolume and thickness) in <i>E. faecalis</i>, whether pathogens or probiotics. NE had less effect on biofilm formation of these bacteria. We also investigated the effect of Epi and NE on adhesion of <i>E. faecalis</i> to eukaryotic cells as it is the first step of colonization of the host. Epi was found to significantly enhance the adhesion of MMH594 and OB15 to Caco-2/TC7 intestinal cells and HaCaT keratinocyte cells, whereas NE significantly increased the adhesion of V583 and Symbioflor 1 DSM 16431 to Caco-2/TC7 cells, the adhesion of MMH594, Symbioflor 1 DSM 16431, and OB15 to HaCaT cells. Analysis of a putative adrenergic sensor of Epi/NE in <i>E. faecalis</i>, compared to QseC, the <i>Escherichia coli</i> adrenergic receptor, allowed the identification of VicK as the nearest protein to QseC with 29% identity and 46% similarity values. Structure modeling and molecular docking of VicK corroborated the hypothesis of possible interactions of this putative adrenergic sensor with Epi and NE, with binding energies of -4.08 and -4.49 kcal/mol, respectively. In conclusion, this study showed for the first time that stress hormones could increase biofilm formation and adhesion to eukaryotic cells in <i>E. faecalis</i>. Future experiments will aim to confirm by <i>in vivo</i> studies the role of VicK as adrenergic sensor in <i>E. faecalis</i> probiotic and pathogen strains. This may help to develop new strategies of antagonism/competition in the gut or skin ecological niches, and to prevent the colonization by opportunistic pathogens.