Migration of Bacteriocins Across Gastrointestinal Epithelial and Vascular Endothelial Cells, as Determined Using In Vitro Simulations

Leané Dreyer,Shelly M Deane,Carine Smith,Anton D Van Staden,Leon M T Dicks

doi:10.1038/s41598-019-47843-9

Leané Dreyer, Shelly M Deane + Show 3 more

Open Access

https://doi.org/10.1038/s41598-019-47843-9

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Journal: Scientific Reports	Publication Date: Aug 7, 2019
Citations: 37	License type: open-access

Affiliation: Stellenbosch University

Abstract

Little is known about the migration of bacteriocins across human cells. In this study, we report on migration of three bacteriocins nisin, plantaricin 423 and bacST4SA across colonic adenocarcinoma (Caco-2) cells and human umbilical vein endothelial cells (HUVECs). Bacteriocins were fluorescently labelled while still maintaining antimicrobial activity. Migration of fluorescently labelled bacteriocins across monolayers was assessed in vitro using transmigration well inserts. After 3 h, 75% of nisin, 85% of plantaricin 423 and 82% of bacST4SA migrated across the Caco-2 cell monolayer. Over the same time span, 88% nisin, 93% plantaricin 423 and 91% bacST4SA migrated across the HUVEC monolayer. The viability of both cell types remained unchanged when exposed to 50 µM of nisin, plantaricin 423 or bacST4SA. The effect of human plasma on bacteriocin activity was also assessed. Activity loss was dependent on bacteriocin type and concentration, with the class-IIa bacteriocins retaining more activity compared to nisin. This is the first report of bacteriocins migrating across simulated gastrointestinal- and vascular-barriers. This study provides some of the first evidence that bacteriocins are capable of crossing the gut-blood-barrier. However, in vivo studies need to be performed to confirm these findings and expand on the role of bacteriocin migration across cell barriers.

Highlights

Experiments conducted on mice have shown that bacteriocins may have beneficial therapeutic properties in vivo
Bacteriocins produced by gut bacteria and able to cross the GBB would enter the circulatory system and as such come into contact with host blood plasma
In a study by Brand et al, 2010, S. aureus Xen 36-infected mice were treated with nisin F, which is similar to nisin A used in this study[9]

Summary

Introduction

Experiments conducted on mice have shown that bacteriocins may have beneficial therapeutic properties in vivo. In vivo bioluminescence studies conducted on mice[28] have shown that L. plantarum 423 and E. mundtii ST4SA, colonise the GIT and prevent L. monocytogenes EGDe from causing systemic infections. BacST4SA (producer: E. mundtii ST4SA), classified as a class IIa bacteriocin, is active against L. monocytogenes, S. aureus and E. faecalis[21,30]. Both bacteriocins bind to target cells by means of electrostatic interactions between positively charged amino acids and negatively charged phospholipids in the cytoplasmic membrane[29,31]

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