# Infection of endothelial cells by Streptococcus agalactiae reveals potential role of PI-2b pilus on endothelial barrier dysfunction

## TL;DR

This study shows how Streptococcus agalactiae weakens blood vessel barriers, especially under stress, and highlights the role of a specific bacterial pilus in causing damage.

## Contribution

The study is the first to show how the PI-2b pilus of Streptococcus agalactiae contributes to endothelial barrier dysfunction under shear stress.

## Key findings

- Shear stress increases adherence of S. agalactiae to endothelial cells and alters VE-cadherin localization.
- PI-2b pilus is essential for optimal disruption of endothelial integrity, especially in the presence of fibrinogen.

## Abstract

Streptococcus agalactiae is responsible for sepsis and meningitis, and the major cause of neonatal morbidity and mortality. However, how S. agalactiae disrupts endothelial barriers is poorly understood.

Analyse the influence of endothelial cell (HUVECs) growth under static and shear stress conditions during infection with S. agalactiae, and the role of pilus PI-2b during endothelial barrier disruption and increased endothelial permeability.

HUVECs under static and shear conditions were infected by S. agalactiae (GBS90356 and GBS90356Δpilus2b) strains in the presence and absence of fibrinogen. VE-cadherin was evaluated by immunofluorescence and RT-PCR assays, and the endothelial permeability by transwell assay.

Shear stress induced the alignment of HUVECs and increased the adherence of S. agalactiae strains (GBS90356 and GBS90356Δpilus2b), mainly in the presence of fibrinogen, in addition to greater peripheral localisation of VE-cadherin. Rupture points and damage to endothelial integrity was visualised after infection with the GBS90356WT strain, mainly in the presence of fibrinogen. RT-PCR analyses identified increase in VE-cadherin expression in HUVECs under shear stress and a decrease in VE-cadherin after infection, with increased levels of endothelial permeability.

Data demonstrate for the first time the dysfunction of the adhesive barrier induced by the S. agalactiae ST-17 strain, mainly in HUVECs under shear stress, where PI-2b expression was essential to optimise the damage to endothelial integrity.